猪源多杀性巴氏杆菌的分子流行病学与致病性研究
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摘要
多杀性巴氏杆菌(Pasteurella multocida,Pm)是一种重要的病原菌,对多种动物和人均有致病性,可引起猪发生肺炎和萎缩性鼻炎(Atrophic rhinitis,AR),也是猪呼吸道疾病综合征(porcine respiratory disease complex,PRDC)的重要致病因子之一。Pm现已流行于世界养猪业发达的各个国家和地区,该病原菌可与多种病原协同感染,从而增加猪群呼吸道疾病的发病率和死亡率,并造成严重的经济损失。本研究对Pm的病原流行病学、分离菌株的生物学特性、分子多样性、耐药现状、毒力和免疫原性基因进行研究,为我国Pm的流行病学研究提供理论依据,为临床上猪巴氏杆菌病的诊断、有效防控和相关的基础研究奠定基础。主要研究内容如下：
1.多杀性巴氏杆菌在我国部分地区猪群中的流行现状
2003-2007年对我国部分地区规模化猪场健康猪群和有肺炎与萎缩性鼻炎疑似症状猪的临床样品进行检测,结果从湖北等16个省、市、自治区2,912份有发病症兆猪的鼻拭子、肺脏、胸腔积液、心血和颈部水肿组织中分离出233株Pm,未能从725份健康猪棉拭子中分离出Pm。在我国猪群中,2003-2007年间Pm的总分离率为8.0%；不同年份Pm的总分离率介于6.4-10.2%之间。应用PCR方法对分离的Pm进行荚膜分型,结果证实,分离株中有92株(39.5%)属A型Pm,128株(54.9%)属D型Pm,1株(0.4%)属B型Pm,12株(5.2%)为未定型分离株。同时对分离的49株Pm进行致病性试验,结果高致病株、中致病株和低致病株分别占受试菌的36.7%(18/49)、49.0%(24/49)和14.3%(7/49)；对分离Pm的产毒素能力进行鉴定,结果11株产毒素多杀性巴氏杆菌(Toxigenic Pasteurella,multocida,T+Pm)均为高致病菌株,占61.1%(11/18)。
2.猪源多杀性巴氏杆菌耐药表型与基因型的研究
对分离的233株Pm菌株进行20种临床常用抗生素的最小抑菌浓度(MICs)试验,结果表明,分离菌株对阿莫西林、林可霉素、克林霉素、四环素和磺胺类药物不敏感,对大观霉素、卡那霉素、庆大霉素和阿米卡星等氨基糖苷类药物中度敏感；而头孢菌素类、氟苯尼考和氟喹诺酮类药物对Pm分离株表现出很高的活性,能有效抑制该类菌群。多重耐药性分析表明,有217株(93.1%)Pm具有多重耐药性；5耐以上的菌株有127株,占54.7%；流行最广的Pm耐药表型为：AMX+LIN+CLI+ TET+SDM+STX。18种耐药基因的PCR检测证实：耐阿莫西林Pm携带blaTEM的阳性率为80.7%；耐林可酰胺类药物Pm携带ermA、ermC和lnuA的阳性率分别为36.7%、49.8%和24.0%；耐甲氧苄啶类Pm携带dfrA5、dfrA7和dfrA13的阳性率分别为18.5%、32.9%和29.5%；而四环素抗性主要由tet(H)、tet(B)和tet(G)介导；磺胺类抗性主要由sull和sul2介导。分析耐药表型与基因型关系表明,同一种抗生素可由不同的耐药基因介导,多数菌株携带有不同的耐药基因,并显著的具有多重耐药性(P<0.01)。
3.猪源多杀性巴氏杆菌的毒力基因型与分布特征研究
对Pm的19种毒力相关基因进行PCR检测,结果证实,粘附因子ptfA(93.6%)、fimA(99.1%)、hsf-2(99.1%),转铁蛋白exbB(99.1%)、exbD(99.1%).tonB(97.9%)、hgbA(96.6%)、fur(92.7%),唾液酸酶nanH97.0%)和外膜蛋白ompA(100%). ompH(93.1%)、oma87(94.4%).plpB(99.1%)的流行与检出率较高,几乎所有的猪源Pm均携带这些毒力因子；而毒力因子pfha,tadD,toxA和pmHAS在猪源Pm菌株中的检出率均低于50%。不同的毒力因子与荚膜血清型具有一定的相关性,如tadD显著的分布于A型Pm(P<0.001)；hsf-1和nanB显著的分布于D型Pm(P<0.001)；hgbA和fur主要分布于A型和D型Pm(P<0.01)；pfha和pmHAS显著的分布于A型和未定型Pm(P<0.001)；且试验中不同地区分离的11株T+Pm的毒素toxA基因也仅分布于D型。
4.猪源多杀性巴氏杆菌分离株的分子多样性研究
采用RAPD,(GTG)5-PCR和Eric-PCR分析方法,对从我国不同地区分离的233株猪源Pm进行核酸分子分型和多样性分析。DNA指纹谱型表明RAPD方法的分辨率为39.48%,多态性条带的百分率为73.96%,可将受试的Pm分为92个基因型,其中有11个(比例为12.0%)为优势谱型。在相似系数为60%时,Pm分离株可被分为32个簇,其中最大的1簇含有A型Pm 20株,D型Pm 22株,B型和未定型Pm各1株,且遗传背景相关的16株海南省分离菌聚集在该簇;11株T+Pm也聚集在该簇。(GTG)5-PCR的分辨率为49.36%,多态性条带的百分率为88.13%,可将受试的Pm分为115个基因型,其中优势谱型有7个(比例为6.08%)。在相似系数为60%时,Pm分离株可被分为68个簇。Eric-PCR指纹分析方法的分辨率为24.46%,多态性条带的百分率为73.46%,可将受试的Pm分为57个基因型,其中优势谱型有11个(比例为19.03%)。在相似系数为60%时,Pm分离株可被分为36个簇。综上分析表明,我国不同地区分离的猪源Pm的核酸基因组存在显著的多样性,同时证明了(GTG)5-PCR和RAPD扩增的DNA指纹比Eric-PCR图谱具有更强的多样性。
5.猪产毒多杀性巴氏杆菌毒素toxA基因的分子特征与致病性研究
为分析我国产毒多杀性巴氏杆菌T+Pm地方分离株的分子特征、遗传背景及毒力特性,对分离的11株T+Pm的毒素toxA基因进行了克隆和测序。结果表明,toxA基因编码的毒素PMT是一个高度保守的蛋白,其核苷酸间的同源性达99%以上,其氨基酸的同源性达98.5%以上,且该基因在911-912和2323-2324核苷酸位点发生点突变的频率较高,达到23.8%(5/21)。对toxA基因的分子进化树分析表明,我国地方T+Pm分离株可分为2个亚群,且菌株间的亲缘关系或遗传背景较近,表现出区域相关性,与韩国、台湾、美国等分离株同属一个进化分支。对小鼠的LD5o试验证实,T+Pm对小鼠具有高致病性,且分离株HN-13表现为强毒力,其对小鼠的LDso为4.25×103CFU。将HN-13株人工感染试验猪,建立T+Pm的感染模型,结果HN-13不但可复制出PAR的临床症状,且该菌株可引起猪肺炎。免疫组织化学分析证实,HN-13株感染猪的急性期,机体中大量的嗜中性白细胞发生局部聚集,以抵抗病原菌的侵入,在肺泡内同时也出现了巨噬细胞吞噬感染的T+Pm,并造成巨噬细胞的坏死和髓样病变。
6.毒素PMT的N-端和C-端蛋白的生物学活性及免疫原性研究
将5个toxA基因片段N1518、C2345、N3172、N3388和C2115分别克隆到合适的原核表达载体pET-28a(b,c)系统,其中pET28a-N1518和pET28b-C2115在大肠杆菌成功表达,获得大小分别为57kDa和78kDa的融合蛋白rPMT-N和rPMT-C,Western blot检测证实这两种表达产物均具有反应原性。分别以200μg rPMT-N和rPMT-C对小白鼠进行体内生物学活性试验,结果两种表达蛋白均不能致死小白鼠；体外细胞毒性试验证实896ng/ml的rPMT-N能使Vero细胞发生病变,而rPMT-C对Vero细胞无明显毒性作用。将rPMT-N和rPMT-C制成亚单位疫苗,同时设天然PMT及无菌PBS对照组,间隔2周分2次免疫小白鼠和仔猪。结果表明rPMT-N、rPMT和天然PMT试验组能诱导小鼠产生较高滴度的毒素抗体,而rPMT-C诱导的毒素抗体滴度较低；对仔猪免疫效力试验证实,rPMT-N、rPMT、rPMT-C和天然PMT均能诱导机体产生针对PMT的毒素抗体,但用1×1010CFU的HN-13株对各组试验仔猪进行鼻腔感染试验后,rPMT-C提供的保护力较rPMT-N、rPMT和天然PMT组低。综上试验表明,rPMT-N具有良好的生物学活性和免疫原性,可作为PAR疫苗添加成分,显示了良好的应用前景。
Pasteurella multocida is an important pathogenic bacterium, which is responsible for various infections in humans and animals. The main diseases associated with this organism in pigs are pneumonic pasteurellosis and atrophic rhinitis. P. multocida is also a contributory agent in porcine respiratory disease complex, a multifactorial disease state increasingly problematic for swine producers. Although the primary disease is important, what's more significant is the fact that this bacteria predisposes to colonization and disease with other viral and bacterial pathogens, resulting in higger morbidity and mortality. This study focused on the pathogen epidemiology, bio-characteristics, antibiograms, virulence genetypes, the pathogenicity of P. multocida, immunogenicity genes, diagnostic method, and two fragments of recombinant subunit P. multocida toxin (rsPMT) were constructed for evaluation as candidate vaccines against progressive atrophic rhinitis (PAR) of swine. The results are as follows.
1. Isolation and identification of P. multocida from pigs and pathogen epidemiology of pasteurellosis in China
The presence of P. multocida in clinical specimens from diseased pigs with pneumonia or atrophic rhinitis from 16 provinces in China between 2003 to 2007 were analyzed, and a total of 233 isolates of Pasteurella multocida were obtained from 2,912 cases of clinical respiratory disease in pigs, giving an isolation rate of 8.0%. The isolation rate at different time points (years) were ranged from 6.4 to 10.2%. Serogroup A P. multocida was isolated from 92 cases (39.5%) and serogroup D isolates from 128 cases (54.9%); twelve isolates (5.2%) were untypable. P. multocida was the fourth most frequent pathogenic bacterium recovered from the respiratory tract, after Streptococcus suis, Haemophilus parasuis and Escherichia coli. The pathogenicities of 49 porcine P. multocida strains isolated from different regions of China were evaluated in mice. Based on mortalities occurring during a 7-day postinoculation period,36.7%,49.0% and 14.3% of 49 isolates were characterized as high, intermediate and low in pathogenicity, respectively. Among them, eleven toxigenic strains of P. multocida of serogroup D isolated from 37 samples of nasal swabs and lesioned lungs from pigs with typical clinical signs of atrophic rhinitis were characterized as high in pathogenicity. These results reveal that P. multocida are widely prevalent in China, and suggest such pathogenic bacteria may play an important role in causing respiratory disease of swine.
2. Phenotypic and genotypic characterization of antimicrobial resistance in P. multocida isolates
Antibiograms and relevant genotypes of porcine P. multocida isolates (n=233) recovered between 2003 and 2007 in China were assessed via broth microdilution test, PCR and sequencing. Among the 20 antimicrobials tested, the most prevalent resistance was to amoxicillin, lincomycin, clindamycin, tetracycline and sulfonamides (ranging from 58.0-96.6%), followed by tilmicosin (28.3%) and aminoglycosides (ranging from 12.0-14.2%). The frequency of antimicrobial resistance among P. multocida isolates from swine in China was higher than that reported from other countries, and 93.1% of the isolates showed multiple resistances,54.7% isolates were resistant to more than five. The most common resistance pattern observed among the isolates was multi-resistance to AMX+LIN+CLI+TET+SDM+STX. There was a progressive increase in multiresistance to more than seven antibiotics, from 16.2% in 2003 to 62.8% in 2007. Resistance profiles suggested that cephalosporins, florfenicol and fluoroquinolone were the drugs most likely to be active against P. multocida. For each antimicrobial agent, amoxicillin resistance was primarily mediated by blaTEM (80.7%), lincosamides resistance by ermA (36.7%), ermC (49.8%) and lnuA (24.0%), trimethoprims resistance by dfrA5 (18.5%), dfrA7 (32.9%) and dfrA13 (29.5%), tetracycline resistance by tet(H), tet(B) and tet(G), and sulfadimidine resistance by sull and sul2. Strains that harbored several genes that conferred resistance to the same antimicrobial agent were often significantly (P< 0.01) more multiresistant than others, and there was positive relation between drug resistance and genetypes. These results provide novel insights into the epidemiological characteristics of porcine P. multocida strains in China, and suggest the need for the prudent use of antimicrobial agents in food animals.
3. The presence and distribution of virulence genes of P.multocida strains from swine
Among the 233 porcine P. multocida isolates, the 19 virulence gene regions ranged in prevalence from 4.7%(toxA) to 100%(ompA). Multiple adhesions (including ptfA, fimA and hsf-2),all iron acquisition factors (exbB, exbD, tonB, hgbA and fur), nanH, and various outer membrane proteins (ompA, ompH, oma87 and plpB) were found each to occur in over 90% of porcine strains. The VFs pfhA, tadD, toxA and pmHAS were present in<50% of strains each. The various VFs exhibited distinctive associations with serogroups, tadD was significantly associated with serogroup A, hsf-1 and nanB were significantly associated with serogroup D, and hgbA and fur were associated with serogroups A and D. The genes pfhA and pmHAS were less common in serogroup D than in other serogroups. It was noted that the toxA gene, which is involved in the pathogenesis of progressive atrophic rhinitis in pigs, was found in only eleven strains, and it was strictly restricted to strains belonging to capsular serogroup D.
4. Molecular diversity of P.multocida isolates from diseased swine in China
A total of 233 porcine P. multocida strains isolated from cases of pneumonia and progressive atrophic rhinitis (PAR) were evaluated for the genotypes and genetic diversity using several DNA fingerprinting methods:RAPD, (GTG) 5-PCR and Eric-PCR. The discriminatory index (CI) for RAPD was 39.48%, and 73.96% distinct bands were identified as polymorphic bands. Analysis of DNA banding patterns generated by RAPD revealed the presence of 92 different genotypes, among which 11 genotypes (12.0%) were preponderant profiling. All isolates could be grouped into 32 clusters at a similarity of 60% after dendrogram analysis. The largest lineage contained 44 strains belonging to serogroup A (20 strains), serogroup D (22 strains), serogroup B (1 strain) and untypable (1 strain), respectively. The discriminatory index for (GTG) 5-PCR was 49.36%, and 88.13% distinct bands were identified as polymorphic bands. These isolates could be divided into 115 different genotypes by their (GTG) 5-PCR fingerprints, among which 7 genotypes (6.08%) were preponderant fingerprints. All isolates could be grouped into 68 clusters at a similarity of 60%. The discriminatory index for Eric-PCR profiling was a relatively low value (CI=24.46%), and 73.46% distinct bands were identified as polymorphic bands. These isolates could be divided into 57 different genotypes by their Eric-PCR fingerprints, among which 11 genotypes (19.03%) were preponderant fingerprints. All isolates could be grouped into 36 clusters at a similarity of 60%. In summary, the results revealed there was significant diversity among analysed strains of porcine P. multocida strains, and suggested that (GTG) 5-PCR and RAPD are highly discriminatory techniques for detecting genetic variation and in epidemiological studies of P. multocida.
5. Molecular characteristics and the pathogenicity of porcine toxigenic P. multocida
In order to analysis the molecular characteristics, genetic background and the pathogenicity of toxigenic P. multocida isolates from swine in China, toxA gene from eleven strains were investigated. Their sequences analyzed here indicated that the P.multocida toxin (PMT) coded by toxA gene is a high conservatism protein. The homology of toxA gene nucleotide sequences of all strains hit above 99%, and the homology of amino acid sequences reached to 98.5% above. However, the nucleotides of toxA gene of five strains,have genesised mutation,in the site 911-912 and 2323-2324. The prevalence and genetic evolution were analyzed based on the toxA gene. We found that there are two highly diverse subgroups among all T+Pm isolates in China. By virulence tests, we found that the HN-13 strain of T+Pm showed high virulence, and the 50% lethal dose (LD50) of HN-13 in mice have been tested to be 4.25×103 CFU intra-abdominal infection. Further, the HN-13 intranasal infection model was also established using piglets. The results showed that there testing piglets not only have the clinical symptom of PAR, but also could cause pneumonia. Immunohistochemistry confirmed that neutrophil could be mobilized to counteracting incursive pathogenic bacteria during acute stage, and macrophagocyte could also participate in the mechanism, inducing cellular necrosis and pulpy pathological changes.
6. Characteristics and immunogenicity of the N-terminal and C-terminal re-combinants of P.multocida toxin
In this study, five fragments of recombinant subunit P.multocida toxin (PMT) were constructed. Only pET28a-N1518 and pET28b-C2115 could be expressed efficiently in Escherichia coli. The molecular weight of the fusion proteins was 57 kDa and 78 kDa. Western blot confirmed that the two proteins could specifically react with an-tiserum against P.multocida toxin. No mice died after the intraperitoneal administration of these two proteins with the dose of 200μg, but Vero cell was pathologically changed after administration of 896ng/mL rPMT-N. The fusion protein of rPMT-N and rPMT-C was purified, and emulsified with Freund's adjuvant in equal volumes to get subunit vaccine. Mice immunized with rPMT-N, rPMT containing rPMT-N and rPMT-C, crude PMT only developed high titers of neutralizing antibodies. However, all piglets were challenged intranasally with 1×1010CFU CFU HN-13 strain of T+Pm. The protection efficiency of rPMT-N, rPMT and crude PMT against HN-13 strain were higher than the group immunized with rPMT-C. The data revealed that the fusion protein of rPMT-N had immunogenicity and potential for developing a subunit vaccine against PAR in pigs.
1.多杀性巴氏杆菌在我国部分地区猪群中的流行现状
2003-2007年对我国部分地区规模化猪场健康猪群和有肺炎与萎缩性鼻炎疑似症状猪的临床样品进行检测,结果从湖北等16个省、市、自治区2,912份有发病症兆猪的鼻拭子、肺脏、胸腔积液、心血和颈部水肿组织中分离出233株Pm,未能从725份健康猪棉拭子中分离出Pm。在我国猪群中,2003-2007年间Pm的总分离率为8.0%；不同年份Pm的总分离率介于6.4-10.2%之间。应用PCR方法对分离的Pm进行荚膜分型,结果证实,分离株中有92株(39.5%)属A型Pm,128株(54.9%)属D型Pm,1株(0.4%)属B型Pm,12株(5.2%)为未定型分离株。同时对分离的49株Pm进行致病性试验,结果高致病株、中致病株和低致病株分别占受试菌的36.7%(18/49)、49.0%(24/49)和14.3%(7/49)；对分离Pm的产毒素能力进行鉴定,结果11株产毒素多杀性巴氏杆菌(Toxigenic Pasteurella,multocida,T+Pm)均为高致病菌株,占61.1%(11/18)。
2.猪源多杀性巴氏杆菌耐药表型与基因型的研究
对分离的233株Pm菌株进行20种临床常用抗生素的最小抑菌浓度(MICs)试验,结果表明,分离菌株对阿莫西林、林可霉素、克林霉素、四环素和磺胺类药物不敏感,对大观霉素、卡那霉素、庆大霉素和阿米卡星等氨基糖苷类药物中度敏感；而头孢菌素类、氟苯尼考和氟喹诺酮类药物对Pm分离株表现出很高的活性,能有效抑制该类菌群。多重耐药性分析表明,有217株(93.1%)Pm具有多重耐药性；5耐以上的菌株有127株,占54.7%；流行最广的Pm耐药表型为：AMX+LIN+CLI+ TET+SDM+STX。18种耐药基因的PCR检测证实：耐阿莫西林Pm携带blaTEM的阳性率为80.7%；耐林可酰胺类药物Pm携带ermA、ermC和lnuA的阳性率分别为36.7%、49.8%和24.0%；耐甲氧苄啶类Pm携带dfrA5、dfrA7和dfrA13的阳性率分别为18.5%、32.9%和29.5%；而四环素抗性主要由tet(H)、tet(B)和tet(G)介导；磺胺类抗性主要由sull和sul2介导。分析耐药表型与基因型关系表明,同一种抗生素可由不同的耐药基因介导,多数菌株携带有不同的耐药基因,并显著的具有多重耐药性(P<0.01)。
3.猪源多杀性巴氏杆菌的毒力基因型与分布特征研究
对Pm的19种毒力相关基因进行PCR检测,结果证实,粘附因子ptfA(93.6%)、fimA(99.1%)、hsf-2(99.1%),转铁蛋白exbB(99.1%)、exbD(99.1%).tonB(97.9%)、hgbA(96.6%)、fur(92.7%),唾液酸酶nanH97.0%)和外膜蛋白ompA(100%). ompH(93.1%)、oma87(94.4%).plpB(99.1%)的流行与检出率较高,几乎所有的猪源Pm均携带这些毒力因子；而毒力因子pfha,tadD,toxA和pmHAS在猪源Pm菌株中的检出率均低于50%。不同的毒力因子与荚膜血清型具有一定的相关性,如tadD显著的分布于A型Pm(P<0.001)；hsf-1和nanB显著的分布于D型Pm(P<0.001)；hgbA和fur主要分布于A型和D型Pm(P<0.01)；pfha和pmHAS显著的分布于A型和未定型Pm(P<0.001)；且试验中不同地区分离的11株T+Pm的毒素toxA基因也仅分布于D型。
4.猪源多杀性巴氏杆菌分离株的分子多样性研究
采用RAPD,(GTG)5-PCR和Eric-PCR分析方法,对从我国不同地区分离的233株猪源Pm进行核酸分子分型和多样性分析。DNA指纹谱型表明RAPD方法的分辨率为39.48%,多态性条带的百分率为73.96%,可将受试的Pm分为92个基因型,其中有11个(比例为12.0%)为优势谱型。在相似系数为60%时,Pm分离株可被分为32个簇,其中最大的1簇含有A型Pm 20株,D型Pm 22株,B型和未定型Pm各1株,且遗传背景相关的16株海南省分离菌聚集在该簇;11株T+Pm也聚集在该簇。(GTG)5-PCR的分辨率为49.36%,多态性条带的百分率为88.13%,可将受试的Pm分为115个基因型,其中优势谱型有7个(比例为6.08%)。在相似系数为60%时,Pm分离株可被分为68个簇。Eric-PCR指纹分析方法的分辨率为24.46%,多态性条带的百分率为73.46%,可将受试的Pm分为57个基因型,其中优势谱型有11个(比例为19.03%)。在相似系数为60%时,Pm分离株可被分为36个簇。综上分析表明,我国不同地区分离的猪源Pm的核酸基因组存在显著的多样性,同时证明了(GTG)5-PCR和RAPD扩增的DNA指纹比Eric-PCR图谱具有更强的多样性。
5.猪产毒多杀性巴氏杆菌毒素toxA基因的分子特征与致病性研究
为分析我国产毒多杀性巴氏杆菌T+Pm地方分离株的分子特征、遗传背景及毒力特性,对分离的11株T+Pm的毒素toxA基因进行了克隆和测序。结果表明,toxA基因编码的毒素PMT是一个高度保守的蛋白,其核苷酸间的同源性达99%以上,其氨基酸的同源性达98.5%以上,且该基因在911-912和2323-2324核苷酸位点发生点突变的频率较高,达到23.8%(5/21)。对toxA基因的分子进化树分析表明,我国地方T+Pm分离株可分为2个亚群,且菌株间的亲缘关系或遗传背景较近,表现出区域相关性,与韩国、台湾、美国等分离株同属一个进化分支。对小鼠的LD5o试验证实,T+Pm对小鼠具有高致病性,且分离株HN-13表现为强毒力,其对小鼠的LDso为4.25×103CFU。将HN-13株人工感染试验猪,建立T+Pm的感染模型,结果HN-13不但可复制出PAR的临床症状,且该菌株可引起猪肺炎。免疫组织化学分析证实,HN-13株感染猪的急性期,机体中大量的嗜中性白细胞发生局部聚集,以抵抗病原菌的侵入,在肺泡内同时也出现了巨噬细胞吞噬感染的T+Pm,并造成巨噬细胞的坏死和髓样病变。
6.毒素PMT的N-端和C-端蛋白的生物学活性及免疫原性研究
将5个toxA基因片段N1518、C2345、N3172、N3388和C2115分别克隆到合适的原核表达载体pET-28a(b,c)系统,其中pET28a-N1518和pET28b-C2115在大肠杆菌成功表达,获得大小分别为57kDa和78kDa的融合蛋白rPMT-N和rPMT-C,Western blot检测证实这两种表达产物均具有反应原性。分别以200μg rPMT-N和rPMT-C对小白鼠进行体内生物学活性试验,结果两种表达蛋白均不能致死小白鼠；体外细胞毒性试验证实896ng/ml的rPMT-N能使Vero细胞发生病变,而rPMT-C对Vero细胞无明显毒性作用。将rPMT-N和rPMT-C制成亚单位疫苗,同时设天然PMT及无菌PBS对照组,间隔2周分2次免疫小白鼠和仔猪。结果表明rPMT-N、rPMT和天然PMT试验组能诱导小鼠产生较高滴度的毒素抗体,而rPMT-C诱导的毒素抗体滴度较低；对仔猪免疫效力试验证实,rPMT-N、rPMT、rPMT-C和天然PMT均能诱导机体产生针对PMT的毒素抗体,但用1×1010CFU的HN-13株对各组试验仔猪进行鼻腔感染试验后,rPMT-C提供的保护力较rPMT-N、rPMT和天然PMT组低。综上试验表明,rPMT-N具有良好的生物学活性和免疫原性,可作为PAR疫苗添加成分,显示了良好的应用前景。
Pasteurella multocida is an important pathogenic bacterium, which is responsible for various infections in humans and animals. The main diseases associated with this organism in pigs are pneumonic pasteurellosis and atrophic rhinitis. P. multocida is also a contributory agent in porcine respiratory disease complex, a multifactorial disease state increasingly problematic for swine producers. Although the primary disease is important, what's more significant is the fact that this bacteria predisposes to colonization and disease with other viral and bacterial pathogens, resulting in higger morbidity and mortality. This study focused on the pathogen epidemiology, bio-characteristics, antibiograms, virulence genetypes, the pathogenicity of P. multocida, immunogenicity genes, diagnostic method, and two fragments of recombinant subunit P. multocida toxin (rsPMT) were constructed for evaluation as candidate vaccines against progressive atrophic rhinitis (PAR) of swine. The results are as follows.
1. Isolation and identification of P. multocida from pigs and pathogen epidemiology of pasteurellosis in China
The presence of P. multocida in clinical specimens from diseased pigs with pneumonia or atrophic rhinitis from 16 provinces in China between 2003 to 2007 were analyzed, and a total of 233 isolates of Pasteurella multocida were obtained from 2,912 cases of clinical respiratory disease in pigs, giving an isolation rate of 8.0%. The isolation rate at different time points (years) were ranged from 6.4 to 10.2%. Serogroup A P. multocida was isolated from 92 cases (39.5%) and serogroup D isolates from 128 cases (54.9%); twelve isolates (5.2%) were untypable. P. multocida was the fourth most frequent pathogenic bacterium recovered from the respiratory tract, after Streptococcus suis, Haemophilus parasuis and Escherichia coli. The pathogenicities of 49 porcine P. multocida strains isolated from different regions of China were evaluated in mice. Based on mortalities occurring during a 7-day postinoculation period,36.7%,49.0% and 14.3% of 49 isolates were characterized as high, intermediate and low in pathogenicity, respectively. Among them, eleven toxigenic strains of P. multocida of serogroup D isolated from 37 samples of nasal swabs and lesioned lungs from pigs with typical clinical signs of atrophic rhinitis were characterized as high in pathogenicity. These results reveal that P. multocida are widely prevalent in China, and suggest such pathogenic bacteria may play an important role in causing respiratory disease of swine.
2. Phenotypic and genotypic characterization of antimicrobial resistance in P. multocida isolates
Antibiograms and relevant genotypes of porcine P. multocida isolates (n=233) recovered between 2003 and 2007 in China were assessed via broth microdilution test, PCR and sequencing. Among the 20 antimicrobials tested, the most prevalent resistance was to amoxicillin, lincomycin, clindamycin, tetracycline and sulfonamides (ranging from 58.0-96.6%), followed by tilmicosin (28.3%) and aminoglycosides (ranging from 12.0-14.2%). The frequency of antimicrobial resistance among P. multocida isolates from swine in China was higher than that reported from other countries, and 93.1% of the isolates showed multiple resistances,54.7% isolates were resistant to more than five. The most common resistance pattern observed among the isolates was multi-resistance to AMX+LIN+CLI+TET+SDM+STX. There was a progressive increase in multiresistance to more than seven antibiotics, from 16.2% in 2003 to 62.8% in 2007. Resistance profiles suggested that cephalosporins, florfenicol and fluoroquinolone were the drugs most likely to be active against P. multocida. For each antimicrobial agent, amoxicillin resistance was primarily mediated by blaTEM (80.7%), lincosamides resistance by ermA (36.7%), ermC (49.8%) and lnuA (24.0%), trimethoprims resistance by dfrA5 (18.5%), dfrA7 (32.9%) and dfrA13 (29.5%), tetracycline resistance by tet(H), tet(B) and tet(G), and sulfadimidine resistance by sull and sul2. Strains that harbored several genes that conferred resistance to the same antimicrobial agent were often significantly (P< 0.01) more multiresistant than others, and there was positive relation between drug resistance and genetypes. These results provide novel insights into the epidemiological characteristics of porcine P. multocida strains in China, and suggest the need for the prudent use of antimicrobial agents in food animals.
3. The presence and distribution of virulence genes of P.multocida strains from swine
Among the 233 porcine P. multocida isolates, the 19 virulence gene regions ranged in prevalence from 4.7%(toxA) to 100%(ompA). Multiple adhesions (including ptfA, fimA and hsf-2),all iron acquisition factors (exbB, exbD, tonB, hgbA and fur), nanH, and various outer membrane proteins (ompA, ompH, oma87 and plpB) were found each to occur in over 90% of porcine strains. The VFs pfhA, tadD, toxA and pmHAS were present in<50% of strains each. The various VFs exhibited distinctive associations with serogroups, tadD was significantly associated with serogroup A, hsf-1 and nanB were significantly associated with serogroup D, and hgbA and fur were associated with serogroups A and D. The genes pfhA and pmHAS were less common in serogroup D than in other serogroups. It was noted that the toxA gene, which is involved in the pathogenesis of progressive atrophic rhinitis in pigs, was found in only eleven strains, and it was strictly restricted to strains belonging to capsular serogroup D.
4. Molecular diversity of P.multocida isolates from diseased swine in China
A total of 233 porcine P. multocida strains isolated from cases of pneumonia and progressive atrophic rhinitis (PAR) were evaluated for the genotypes and genetic diversity using several DNA fingerprinting methods:RAPD, (GTG) 5-PCR and Eric-PCR. The discriminatory index (CI) for RAPD was 39.48%, and 73.96% distinct bands were identified as polymorphic bands. Analysis of DNA banding patterns generated by RAPD revealed the presence of 92 different genotypes, among which 11 genotypes (12.0%) were preponderant profiling. All isolates could be grouped into 32 clusters at a similarity of 60% after dendrogram analysis. The largest lineage contained 44 strains belonging to serogroup A (20 strains), serogroup D (22 strains), serogroup B (1 strain) and untypable (1 strain), respectively. The discriminatory index for (GTG) 5-PCR was 49.36%, and 88.13% distinct bands were identified as polymorphic bands. These isolates could be divided into 115 different genotypes by their (GTG) 5-PCR fingerprints, among which 7 genotypes (6.08%) were preponderant fingerprints. All isolates could be grouped into 68 clusters at a similarity of 60%. The discriminatory index for Eric-PCR profiling was a relatively low value (CI=24.46%), and 73.46% distinct bands were identified as polymorphic bands. These isolates could be divided into 57 different genotypes by their Eric-PCR fingerprints, among which 11 genotypes (19.03%) were preponderant fingerprints. All isolates could be grouped into 36 clusters at a similarity of 60%. In summary, the results revealed there was significant diversity among analysed strains of porcine P. multocida strains, and suggested that (GTG) 5-PCR and RAPD are highly discriminatory techniques for detecting genetic variation and in epidemiological studies of P. multocida.
5. Molecular characteristics and the pathogenicity of porcine toxigenic P. multocida
In order to analysis the molecular characteristics, genetic background and the pathogenicity of toxigenic P. multocida isolates from swine in China, toxA gene from eleven strains were investigated. Their sequences analyzed here indicated that the P.multocida toxin (PMT) coded by toxA gene is a high conservatism protein. The homology of toxA gene nucleotide sequences of all strains hit above 99%, and the homology of amino acid sequences reached to 98.5% above. However, the nucleotides of toxA gene of five strains,have genesised mutation,in the site 911-912 and 2323-2324. The prevalence and genetic evolution were analyzed based on the toxA gene. We found that there are two highly diverse subgroups among all T+Pm isolates in China. By virulence tests, we found that the HN-13 strain of T+Pm showed high virulence, and the 50% lethal dose (LD50) of HN-13 in mice have been tested to be 4.25×103 CFU intra-abdominal infection. Further, the HN-13 intranasal infection model was also established using piglets. The results showed that there testing piglets not only have the clinical symptom of PAR, but also could cause pneumonia. Immunohistochemistry confirmed that neutrophil could be mobilized to counteracting incursive pathogenic bacteria during acute stage, and macrophagocyte could also participate in the mechanism, inducing cellular necrosis and pulpy pathological changes.
6. Characteristics and immunogenicity of the N-terminal and C-terminal re-combinants of P.multocida toxin
In this study, five fragments of recombinant subunit P.multocida toxin (PMT) were constructed. Only pET28a-N1518 and pET28b-C2115 could be expressed efficiently in Escherichia coli. The molecular weight of the fusion proteins was 57 kDa and 78 kDa. Western blot confirmed that the two proteins could specifically react with an-tiserum against P.multocida toxin. No mice died after the intraperitoneal administration of these two proteins with the dose of 200μg, but Vero cell was pathologically changed after administration of 896ng/mL rPMT-N. The fusion protein of rPMT-N and rPMT-C was purified, and emulsified with Freund's adjuvant in equal volumes to get subunit vaccine. Mice immunized with rPMT-N, rPMT containing rPMT-N and rPMT-C, crude PMT only developed high titers of neutralizing antibodies. However, all piglets were challenged intranasally with 1×1010CFU CFU HN-13 strain of T+Pm. The protection efficiency of rPMT-N, rPMT and crude PMT against HN-13 strain were higher than the group immunized with rPMT-C. The data revealed that the fusion protein of rPMT-N had immunogenicity and potential for developing a subunit vaccine against PAR in pigs.
引文
1. 蔡宝祥,殷震,谢三星.动物传染病诊断学.南京：江苏科学技术出版社,1992
2. 白新盛. 畜禽重大疫病生物技术防制研究.北京：中国农业科技出版社,1998
3. 陈焕春.规模化猪场疫病控制与净化.北京：中国农业出版社,2000：260-265
4. 常丙功,李红,石朝辉,张丽芳,刘星,张远富.用随意扩增多态性DNAPCR方法检查实验小鼠的嗜肺性巴氏杆菌.中华微生物学和免疫学杂志,2001,21(6)：694
5. 崔尚金.猪传染性萎缩性鼻炎流行特点、危害状况、诊断与防治净化.猪业科学,2009,6：22-28
6. 戴自英.临床抗菌药物学.北京：人民卫生出版社,1985
7. 东秀珠,蔡妙英.常见细菌系统鉴定手册.北京：科学出版社,2001,9-348
8. F.奥斯伯,R.布伦特,R.E.金斯顿,等著.精编分子生物学实验指南.北京：科学出版社,1998,366-370
9. 范玉霞.猪萎缩性鼻炎的防治对策.动物医学进展,2006,25(5)：114-116
10.甘肃农业大学主编.兽医微生物学实验指导.北京：农业出版社,1980：1-31
11.国际兽疫局编著.诊断试剂和疫苗标准手册.青岛新闻出版局,1996.
12.管宇,沈志强,刘吉山,庞万勇,王燕,莫玲.应用16S rRNA基因测序法鉴定禽多杀性巴氏杆菌的研究.中国预防兽医学报,2003,25(5)：349-352
13.黄显会,陈杖榴,张淑婷,曾振灵.禽多杀性巴氏杆菌感染对麻保沙星在鸡体内药动学特征的影响研究.畜牧兽医学报,2003,34(1)：98-102
14.纪剑飞,张成刚.包涵体重组蛋白的纯化及复性.沈阳药科大学学报,1998,15(4)：303-307
]5.金天明, 高丰,佟庆彬,武迎红.巴氏杆菌对链霉素和磺胺耐药机制的研究.畜牧与兽医,2007,39(3)：5-7
16.金天明,武迎红,李向阳,刘海学,王学理,冯海华,高丰.巴氏杆菌耐药性检测芯片的研制.畜牧与兽医,2008,40(9)：74-75
17.刘杰,杨建德,刘文周,孔宪刚.猪萎缩性鼻炎研究进展.中国兽医杂志,2003,39(11)：30-32
18.刘杰,杨建德,孔宪刚,刘文周.多杀巴氏杆菌毒素的研究进展.畜牧兽医科技信息,2002,2(05)：17-20
19.刘建杰,吴斌,陈焕春.猪萎缩性鼻炎产毒多杀性巴氏杆菌的研究进展.动物医学进展,2002,23(1)：10-13
20.卢圣栋主编.现代分子生物学实验技术.第二版,北京：中国协和医科大学出版社,1999
21.鲁承,金鑫,杨咏洁.多重PCR在猪传染性萎缩性鼻炎诊断中的应用.中国兽医科技,2003,39(12)：7-9
22.陆承平.兽医微生物学(第三版).北京：中国农业出版社,2001：249-254
23.李雪,金莉莉,王秋.病原微生物分子分型技术研究进展.中国公共卫生,2007,23(3)：373-374
24.马俊英,刘健华,陈杖榴,曾振灵.细菌分型的分子生物学技术研究进展.中国兽医科学,2007,37(10)：914-918
25.倪语星,洪秀华.细菌耐药性监测与抗感染治疗.北京：人民军医出版社,2002
26.萨姆布鲁克J,弗里奇E F,曼尼阿蒂斯T著,金冬雁,黎孟枫等译.分子克隆实验指南(第二版).北京：科学出版社,1996
27.沈关心,周汝麟主编.现代免疫学实验技术.武汉:湖北科学技术出版社,1998,112-119
28.斯特劳.B.E,阿莱尔.S.D,蒙加林.W.L,泰勤.D.J主编.猪病学(第八版).赵德民,张中秋,沈建忠主译,狄伯雄,甘孟侯主校.北京：中国农业大学出版社,2000
29.汤锦如,阮宪章,汪辰生等,猪传染性萎缩性鼻炎诊断研究报告.中国兽医杂志,1981,7(9)：9-11
30.唐先春,吴斌,陈焕春等.猪产毒多杀性巴氏杆菌研究进展.动物医学进展,2003,10(5)：14-17
31.唐先春,吴斌,陈焕春等.猪多杀性巴氏杆菌PCR诊断方法的建立与应用.中国兽医科技,2004,2(2)：46-48
32.唐先春,吴斌,刘国平等.应用双重PCR检测产毒素多杀性巴氏杆菌.中国兽医学报,2005,25(4)：374-375
33.汪家政,范明.蛋白质技术手册.北京：科学出版社,2000
34.魏洁.检测产毒多杀性巴氏杆菌毒素抗体乳胶凝集试验方法的研究.[硕士学位论文].武汉：华中农业大学图书馆,2005
35.吴斌,陈焕春,何启盖.应用乳胶凝集实验进行猪传染性萎缩性鼻炎血清流行病学调查.中国兽医科技,2001,31(6)：21-22
36.吴斌,唐先春,陈焕春,王大鹏.猪源多杀性巴氏杆菌ompH基因的克隆、表达.畜牧兽医学报,2005,36(7)：701-704
37.吴范庚.我国多杀性巴氏杆菌血清学鉴定及交互免疫试验.中国兽医杂志,1997,23(8)：14-15
38.王大鹏,吴斌,周锐等.猪源D型产毒素多杀性巴氏杆菌toxA基因的克隆与表达.中国兽医学报,2006,26(3)：271-273
39.杨留战,苑士祥,张树成等.产毒多杀性巴氏杆菌和支气管败血波氏杆菌在猪萎缩性鼻炎中的流行病学研究.中国兽医科技,1992,7(22)：3-5
40. Aarestrup F M. Association between the consumption of antimicrobial agents in animal husbandry and the occurrence of resistant bacteria among food animals. Int J Antimicrob Agents,1999,12,279-285
41. Aarestrup F M, Seyfarth A M, Angen 0. Antimicrobial susceptibility of Haemophilus parasuis and Histophilus somni from pigs and cattle in Denmark. Vet Microbiol,2004,101: 143-146
42. Abdoulaye BN. Manual of diagnostic tests and vaccines for terrestrial animals,5th edition, NY:the OIE International Committee,2004
43. Adler B, Bulach D, Chung J, Doughty S, Hunt M, Rajakumar K, Serrano M, van Zanden A, Zhang Y, Ruffolo C. Candidate vaccine antigens and genes in Pasteurella multocida. J. Biotechnol,1999,73:83-90
44. Al-haj Ali H, Sawada T, Hatakeyama H, Katayama Y, Ohtsuki N, Itoh O. Invasion of chicken embryo fibroblast cells by avian Pasteurella multocida. Vet Microbiol,2004,104:55-62
45. Amigot J A, Torremorell M, Pijoan C. Evaluation of techniques for the detection of toxigenic Pasteurella multocida strain from pigs. J Vet Diagn Invest,1998,10(2): 169-173.
46. Amonsin A, Wellehan J F, Li L L, Laber J, Kapur V. DNA fingerprinting of Pasteurella multocida recovered from avian sources. JClin Microbiol.2002,40(8):3025-3031
47. Arashima Y, Kumasaka K. Pasteurellosis as zoonosis. Intern Med,2005,44:692-693
48. Backstrom L R, Brim T A, Collins M T. Development of turbinate lesions and nasal colonization of Bordetella bronchiseptica and Pasteurella multocida during long term exposure of healthy pigs affected by atrophic rhinitis. Can J Vet Res,1988,52:23-29
49. Baekbo P. Pathogenic properties of Pasteurella multocida in the lungs of pigs; the significance of toxin production. Proceedings of the International Pig Veterinary Society, 1988,10:58
50. Bagley K C, Abdelwahab S F, Tuskan RG. Pasteurella multocida toxin activates human monocyte-derived and murine bone marrow-derived dendritic cells in vitro but suppresses antibody production in vivo. Infect Immun,2005,73(1):413-421
51. Baldwin M R, Lakey J H, Lax A J. Identification and characterization of the Pasteurella multocida toxin translocation domain. Mol Microbiol,2004,54(1):239-250
52. Bethe A, Wieler LH, Selbitz HJ, Ewers C. Genetic diversity of porcine Pasteurella multocida strains from the respiratory tract of healthy and diseased swine. Vet Microbiol,2009, 139(1-2):97-105
53. Blackall P J, Pahoff J L, Bowles R. Phenotypic characterisation of Pasteurella multocida isolates from Australian pigs.Vet microbiol,1997,57(4):355-360
54. Blackall P J, Miflin J K. Identification and typing of Pasteurella multocida:a review. Avian Pathol,2000,29(4):271-87
55. Bosch M, Garrido E, Llagostera M, de Rozas A M P, Badiola I, Barbe J. Pasteurella multocida exbB, exbD and tonB genes are physically linked but independently transcribed. FEMS Microbiol Lett,2002,210:201-208
56. Borrathybay E, Sawada T, Kataoka Y, Ohtsu N, Takagi M, Nakamura S, Kawamoto E A 39 kDa protein mediates adhesion of avian Pasteurella multocida to chicken embryo fibroblast cells. Vet Microbiol,2003,97:229-243
57. Bousquet E, Morvan H, Aitken I, Morgan J H. Comparative in vitro activity of doxycycline and oxytetracycline against porcine respiratory pathogens. Veterinary Record,1997,141: 37-40
58. Boyce J D, Adler B. The capsule is a virulence determinant in the pathogenesis of Pasteurella multocida M1404(B:2). Infect Immun,2000,68:3463-3468
59. Boyce J D, Chung J Y, Adler B. Pasteurella multocida capsule:composition, function and genetics. JBiotechnol,2000,83:153-160
60. Boyce J D, Cullen P A, Nguyen V, Wilkie I, Adler B. Analysis of the Pasteurella multocida outer membrane subproteome and its response to the in vivo environment of the natural host. Proteomics,2006,6:870-880
61. Bowersock T L, Hooper T, Pottenger R. Use of ELISA to detect toxigenic Pasteurella multocida in atrophic rhinitis in swine. J Vet Diagn Invest,1992,4(3):419-422
62. Bowles R E, Pahoff J L, Smith B N, Blackall P J. Ribotype diversity of porcine Pasteurella multocida from Australia. Aust Vet J.2000,78(9):630-635
63. Brockmeier S L, Register K B. Effect of temperature modulation and bvg mutation of Bordetella bronchiseptica on adhesion, intracellular survival and cytotoxicity for swine alveolar macrophages. Vet Microbiol,2000,73:1-12
64. Brockmeier S L, Palmer M V, Bolin S R, Rimler R B. Effects of intranasal inoculation with Bordetella bronchiseptica, porcine reproductive and respiratory syndrome virus, or a combination of both organisms on subsequent infection with Pasteurella multocida in pigs. American Journal of Veterinary Research,2001,62:521-525
65. Brockmeier S L, Halbur P G, Thacker E L. Porcine respiratory disease complex. In:Borgden KA, Guthmiller JM, editors. Polymicrobial diseases. Washington, DC:ASM,2002.
66. Brockmeier S L. Prior infection with Bordetella bronchiseptica increases nasal colonization by Haemophilus parasuis in swine. Vet Microbiol.2004,99(1):75-78
67. Bronzwaer S L, Cars O, Buchholz U, Molstad S, Goettsch W, Veldhuijzen I K, Kool J L, Sprenger M J, Degener J E. A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerg Infect Dis,2002,8:278-282
68. Brogden K A, Nordholm G, Ackermann M. Antimicrobial activity of cathelicidins BMAP28, SMAP28, SMAP29, and PMAP23 against Pasteurella multocida is more broad-spectrum than host species specific. Vet Microbio,2007,119:76-81
69. Cai X, Chen H, Blackall P J, Yin Z, Wang L, Liu Z, Jin M. Serological characterization of Haemophilus parasuis isolates from China. Vet Microbiol,2005,111:231-236
70. Carvalho LFOS, Segales J, Pijoan C. Effect of porcine reproductive and respiratory syndrome virus on subsequent Pasteurella multocida challenge in pigs. Vet Microbiol,1997, 55:241-246
71. Casarez E A, Pillai S D, Mott J B, Vargas M, Dean K E, Di Giovanni G D. Direct comparison of four bacterial source tracking methods and use of composite data sets. J Appl Microbiol, 2007,103(2):350-364
72. Caprioli A, Busani L, Martel J L, Helmuth R. Monitoring of antibiotic resistance in bacteria of animal origin:epidemiological and microbiological methodologies. Int J Antimicrob Agents,2000,14:295-301
73. Carter G R. Studies on Pasteurella multocida I. A haemagglutination test for the identification of serological types. Am J Vet Res,1955,16:481-484
74. Carter GR. Pasteurellosis:Pasteurella multocida and Pasteurella haemolytica. Adv Vet Sci, 1967,11:321-379
75. Carter G R, Chengappa M M. Hyaluronidase production by type B Pasteurella multocida from cases of hemorrhagic septicemia. J Clin Microbiol,1980,11:94-96
76. Chandrasekaran S, Yeap P C. Pasteurella multocida in pigs:The serotypes and the assessment of their virulence in mice. Br Vet J,1982,138:332-336
77. Chang W H, Carter G R. Multiple drug resistance in Pasteurella multocida and Pasteurella haemolytica from cattle and swine. Journal of the American Veterinary Medical Association, 1976,169:710-712
78. Chansiripornchai N, Ramasoota P, Sasipreeyajan J, Svenson S B. Differentiation of avian pathogenic Escherichia coli (APEC) strains by random amplified polymorphic DNA (RAPD) analysis. Vet Microbiol,2001,80(1):75-83
79. Chanter N, Rutter J M, Luther P D. Rapid detection of toxigenic Pasteurella multocida by an agar overlay method. Vet Rec,1986,119(3):629-630
80. Chanter N, Rutter JM. Pasteurellosis in pigs and the determinants of cirulence of toxigenic Pasteurella multocida. London:Academic Press,1989.
81. Chanter N, Magyar T, Rutter JM. Interactions between Bordetella bronchiseptica and toxigenic Pasteurella multocida in atrophic rhinitis of pigs. Res Vet Sci,1989,47(1):48-53
82. Chih-Ming Liao, Chienjin Huang,Shih-Ling Hsuan. Immunogeniciti and efficacy of three recombinant subunit Pasteurella multocida. toxin vaccines against progressive atrophic rhinitis in pigs. Vaccine,2006; 24(2):27-35
83. Choi C, Chae C. Enhanced Detection of Toxigenic Pasteurella multocida Directly from Nasal Swabs Using a Nested Polymerase Chain Reaction. Vet J,2001,162(6):255-258
84. Choi C, Kim B, Cho W S, Kim J, Kwon D, Cheon D S, Chae C. Capsular serotype, toxA gene, and antimicrobial susceptibility profiles of Pasteurella multocida isolated from pigs with pneumonia in Korea. Veterinary Record,2001,149:210-212
85. Choi-Kim K, Maheswaran S K, Felice L J, Molitor T. W. Relationship between the iron regulated outer membrane proteins and the outer membrane proteins of in vivo grown Pasteurella multocida. Vet Microbiol,1991,28:75-92
86. Chung J Y, Wilkie I,Boyce J D, Townsend K M, Frost A J, Ghoddusi M, Adler B. Role of capsule in the pathogenesis of fowl cholera caused by Pasteurella multocida serogroup A. Infect Immun,2001,69:2487-2492
87. Chung J Y, Wilkie I, Boyce J D, Adler B. Vaccination against fowl cholera with acapsular Pasteurella multocida A:1.Vaccine,2005,23:2751-2755
88. Ciprian A, Pijoan C, Cruz T, Camacho J, Totora J, Colmenares G, Lopez-Revilla R and de la Garza M. Mycoplasma hyopneumoniae increases the susceptibility of pigs to experimental Pasteurella multocida pneumonia. Canadian Journal of Veterinary Research,1988,52: 434-438
89. Cote S, Harel J, Higgins R, Jacques M. Resistance to antimicrobial agents and prevalence of R plasmids in Pasteurella multocida from swine. American Journal of Veterinary Research, 1991,52:1563-1567
90. Cowart R P, Backstrom L, Brim T A. Pasteurella multocida and Bordetella bronchiseptica in atrophic rhinitis and pneumonia in swine. Can J Vet Res,1989,53(2):295-300
91. Cundell D R, Gerard N P, Gerard C, Idanpaan-Heikkila I, Tuomanen E I. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature,1995,377:435-438
92. Dabo S M, Confer A W, Quijano-Blas R A. Molecular and immunological characterization of Pasteurella multocida serotype A:3 OmpA:evidence of its role in P. multocida interaction with extracellular matrix molecules. Microb Pathog.2003,35:147-157
93. Dabo S M, Confer A W, Hartson S D. Adherence of Pasteurella multocida to fibronectin. Vet Microbiol,2005,110:265-275
94. Davies R L, MacCorquodale R, Baillie S, Caffrey B. Characterization and comparison of Pasteurella multocida strains associated with porcine pneumonia and atrophic rhinitis. J Med Microbiol,2003,52:59-67
95. Davies R L, MacCorquodale R, Reilly S. Characterisation of bovine strains of Pasteurella multocida and comparison with isolates of avian, ovine and porcine origin. Vet Microbiol, 2004,99:145-158
96. DeAngelis P L. Enzymological characterization of the Pasteurella multocida hyaluronic acid synthase. Biochemistry,1996,35:9768-9771
97. DeAngelis P L and Padgett-McCue A J. Identification and molecular cloning of a chondroitin synthase from Pasteurella multocida type F.JBiol Chem,2000,275:24124-24129
98. DeAngelis P L, White C L. Identification and molecular cloning of a heparosan synthase from Pasteurella multocida type D. JBiol Chem,2002,277:7209-7213
99. DeAngelis P L, White C L. Identification of a distinct, cryptic heparosan synthase from Pasteurella multocida types A, D, and F. J Bacteriol,2004,186:8529-8532
100. Diwan N, Bhagwat A A, Bauchan G B, Cregan P B. Simple sequence repeat DNA markers in alfalfa and perennial and annual Medicago species. Genome,1997,40(6):887-895
101. Djordjevic S P, Eamens G J, Ha H, Walker M J, Chin J C. Demonstration that Australian Pasteurella multocida isolates from sporadic outbreaks of porcine pneumonia are non-toxigenic (toxA-) and display heterogeneous DNA restriction endonuclease profiles compared with toxigenic isolates from herds with progressive atrophic rhinitis. J Med Microbiol,1998,47:679-688
102. Dominick M A, Rimler RB. Turbinate atrophy in gnotobiotic pigs intranasally inoculated with protein toxin isolated from type D Pasteurella multocida. J Vet Res,1986,47(7): 1532-1536
103. Dominick M A, Rimler R B. Turbinate osteoporosis in pigs following intranasal inoculation of purified Pasteurella toxin:histomorphometric and ultrastructural studies. Vet Pathol,1988, 25(1):17-27
104. Doughty S W, Ruffolo C G, Adler B. The type 4 fimbrial subunit gene of Pasteurella multocida. Vet Microbiol,2000,72:79-90
105. Drzeniek R, Scharmann W, Balke E. Neuraminidase and N-acetylneuraminate pyruvate-lyase of Pasteurella multocida. JGen Microbiol,1972,72:357-368
106. Dugal F, Belange M, Jacques M. Enhanced adherence of Pasteurella multocida to porcine tracheal rings preinfected with Bordetella bronchiseptica. Can J Vet Res,1992,56:260-264
107. Dziva F, Muhairwa A P, Bisgaard M, Christensen H. Diagnostic and typing options for investigating diseases associated with Pasteurella multocida, Vet Microbiol,2008,128:1-22
108. Elias B, Kruger M, P Gergely, R Voets, and P Rafai. Interaction between immunity to Bordetella bronchiseptica and infection of pig herds by Bordetella bronchiseptica and Pasteurella multocida. J Vet Med Sci,1996,55(2):617-622
109. Ewers C, Lubke-Becker A, Bethe A, Kiebling S, Filter M, Wieler L H. Virulence genotype of Pasteurella multocida strains isolated from different hosts with various disease status. Vet Microbiol,2006,114:304-317
110. Fernandez de Henestrosa A R, Badiola I, Saco M, Perez de Rozas A M, Campoy S, Barbe J. Importance of the galE gene on the virulence of Pasteurella multocida. FEMS Microbiol Lett, 1997,154:311-316
111. Finco-Kent D L, Galvin J E, Suiter B T. Pasteuella multocida toxin type D serological assay as an alternative to the toxin neutralization lethality test in mice. Biologicals,2001,29,7-10
112. Foged N T, Nielsen J P, Pederson K B. Differention of toxigenic Pasteurella multocida from nontoxigenic isolates of Pasteurella multocida by Enzyme-linked Immunosorbent Assay. J Clin Microbiol,1988,26(7):1419-1420
113. Foged N T, Nielsen J P, Jorsal S. Protection against progressive atrophic rhinitis by vaccination with Pasteurella multocida toxin purified by monoclonal antibodies. Vet Rec, 1989,125(1):7-11
114. Frank G H. Pasteurellosis of Cattle. In:Pasteurella and Pasteurellosis, Academic Press Limited, London.1989
115. Fuentes M and Pijoan C. Pneumonia in pigs induced by intranasal challenge exposure with pseudorabies virus and Pasteurella multocida. American Journal of Veterinary Research, 1987,48:1446-1448
116. Fuller TE, Kennedy M J, Lowery D E. Identification of Pasteurella multocida virulence genes in a septicemic mouse model using signature-tagged mutagenesis. Microb Pathog, 2000,29:25-38
117. Fussing V, Nielsen J P, Bisgaard M, Meyling A. Development of a typing system for epidemiological studies of porcine toxin-producing Pasteurella multocida ssp. multocida in Denmark. Vet Microbiol,1999,65(1):61-74
118. Galdiero M, Folgore A, Nuzzo I, Galdiero E. Neutrophil adhesion and transmigration through bovine endothelial cells in vitro by protein H and LPS of Pasteurella multocida. Immunobiology,2000,202:226-238
119. Gamage L N A, Wijewardana T G, Bastiansz H L G and Vipulasiri A A. An outbreak of acute pasteurellosis in swine caused by serotype B:2 in Sri Lanka. Sri Lanka Veterinary Journal, 1995,42:15-19
120. Gilmour N J L. Pasteurellosis in sheep. Vet Rec,1978,102:100-102
121. Glisson J R,Contreras M D, Cheng I H N, Wang C. Crossprotection studies with Pasteurella multocida bacterins prepared from bacteria propagated in iron-depleted medium. Avian Dis, 1993,37:1074-1079
122. Glorioso J C, Jones G W, Rush H G, Pentler L J, Darif C A, Coward J E. Adhesion of type A Pasteurella multocida to rabbit pharyngeal cells and its possible role in rabbit respiratory tract infections. Infect Immun,1982,35:1103-1109
123. Gois M, Sisak F, Kuksa F, Sovadina M. Incidence and evaluation of the microbial flora in the lungs of pigs with enzootic pneumonia. Zentralblatt fur Veterinarmedizin,1975,22: 205-219.
124. Gray-Owen S D, Schryvers A B. Bacterial transferrin and lactoferrin receptors. Trends Microbiol,1996,4:185-191
125. Gutierrez Martin C B, Rodriguez Ferri E F. In vitro susceptibility of Pasteurella multocida subspecies multocida strains isolated from swine to 42 antimicrobial agents. Zbl Bakt,1993, 279:387-393
126. Halbur P, Opriessnig T, Yaeger M, Yoon K-J. Case trends at the Iowa State University Veterinary Diagnostic Laboratory (ISU-VDL). Proceedings of Alpharma Technical Meeting on Swine Diseases, St. Hyacinth, Quebec and London, Ontario,2006,20-21
127. Hansen L M, Blanchard P C, Hirsh D C. Distribution of tet(H) among Pasteurella isolates from the United States and Canada. Antimicrobial Agents and Chemotherapy,1996,40: 1558-1560
128. Harmon B G, Glisson J R, Latimer K S, Steffens W L, Nunnally J C. Resistance of Pasteurella multocida A:3,4 to phagocytosis by turkey macrophages and heterophils. Am J Vet Res,1991,52:1507-1511
129. Harper M, Boyce J D, Wilkie I W, Adler B. Signaturetagged mutagenesis of Pasteurella multocida identifies mutants displaying differential virulence characteristics in mice and chickens. Infect Immun,2003,71:5440-5446
130. Harper M, Cox A D, St Michael F, Wilkie I W, Boyce J D, Adler B. A heptosyltransferase mutant of Pasteurella multocida produces a truncated lipopolysaccharide structure and is attenuated in virulence. Infect Immun,2004,72:3436-3443
131. Harper M, Boyce J D, Adler B. Pasteurella multocida pathogenesis:125 years after Pasteur. FEMS Microbiol Lett,2006,265:1-10
132. Heddleston K L, Watko L P, Rebers P A. Dissociation of a fowl cholera strain of Pasteurella multocida. Avian Dis,1964,8:649-657
133. Heddleston K L, Gallagher J E, Rebers P A. Fowl cholera:gel diffusion precipitin test for serotyping Pasteurella multocida from avian species. Avian Dis,1972,16:925-936
134.Hoskins IC, Thomas L H, Lax A J. Nasal infection with Pasteurella multocida causes proliferation of bladder epithelium in gnotobiotic pigs. Vet Rec,1997,140,22
135. Hunt M L, Adler B, Townsend K M. The molecular biology of Pasteurella multocida. Vet Microbiol,2000,72:3-25
136. Hunt M L, Boucher D J, Boyce J D, Adler B. In vivo-expressed genes of Pasteurella multocida. Infect Immun,2001,69:3004-3012
137. Hueppe F I. Ueber die Wildseuche und ihre Bedeutung fu"r die Nationalo konomie und die Hygiene.Berliner Klinische Wochenschrift,1886,44 (11):753-758
138. Inzana, T J, Todd, J, Ma J, Veit H. Characterisation of a non-hemolytic mutant of an Actinobacillus pleuropneumoniae serotype 5:role of 110 kDa hemolysin in virulence and immunoprotection. Microb Pathog,1991,10:281-296
139. Isaacson R E, Trigo E. Pili of Pasteurella multocida of porcine origin. FEMS Microbiol Lett, 1995,132:247-251
140. Jamaludin R, Blackall P J, Hansen M F, Humphrey S, Styles M. Phenotypic and genotypic characterisation of Pasteurella multocida isolated from pigs at slaughter in New Zealand. N Z Vet J,2005,53:203-207
141. Johnson R B, Dawkins H J S, Spencer T L. Electrophoretic profiles of Pasteurella multocida isolates from animals with haemorrhagic septicaemia. Am J Vet Res,1991,52:1644-1648
142. Jordan D, Hoffman L, Thacker E. Pasteurella multocida as a component of porcine respiratory disease complex (PRDC). Proceedings of the American Association of Swine Practitioners,2006,149-152
143. Jordan R W, Hamilton T D, Hayes C M. Modulation of the humoral immune response of swine and mice mediated by toxigenic Pasteurella multocida. FEMS Immunol Med Microbiol, 2003,39(1):51-59
144. Kachlany S C, Planet P J,DeSalle R, Fine D H, Figurski D H, Kaplan J B. Flp-1, the first representative of a new pilin gene subfamily, is required for non-specific adherence of Actinobacillus actinomycetemcomitans. Mol Microbiol,2001,40:542-554
145. Kamp E M, Bokken G C, Vermeulen T M. A specific and sensitive PCR assay suitable for large scale detection of toxigenic Pasteurella multocida in nasal and tonsillar swabs specimes of pigs. J Vet Diagn Invest,1996,8(1):304-309
146. Kehrenberg C, Schulze-Tanzil G, Martel J L, Chaslus-Dancla E, Schwarz S. Antimicrobial resistance in pasteurella and mannheimia:epidemiology and genetic basis. Vet Res,2001,32: 323-339
147. Kehrenberg C, Mumme J, Wallmann J, Verspohl J, Tegeler R, Kuhn T, Schwarz SMonitoring of florfenicol susceptibility among bovine and porcine respiratory tract pathogens collected in Germany during the years 2002 and 2003. Journal of Antimicrobial Chemotherapy,2004, 54:572-574
148. Kehrenberg C and Schwarz S. Plasmid-borne florfenicol resistance in Pasteurella multocida. Journal of Antimicrobial Chemotherapy,2005,55:773-775
149. Kengo Kitadokoro, Shigeki Kamitani, Aya Fukui, Hiromi Toshima,Masami Miyake, Yasuhiko Horiguchi. Structure and function of C-terminal catalytic region of Pasteurella multocida toxin. BMC Proceedings,2007,104(12):5139-5144
150. Killgore G, Thompson A, Johnson S, Brazier J, Kuijper E, Pepin J, Frost E H, Savelkoul P, Nicholson B, van den Berg R J, Kato H, Sambol S P, Zukowski W, Woods C, Limbago B, Gerding D N, McDonald L C. Comparison of seven techniques for typing international epidemic strains of Clostridium difficile:restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing. JClin Microbiol,2008,46(2):431-437
151. Kimura A, Mountzouros K T, Relman D A, Falkow S, Cowell J L. Bordetella pertussis filamentous hemagglutinin:evaluation as a protective antigen and colonization factor in a mouse respiratory infection model. Infect Immun,1990,58:7-16
152. Lax A J, Chanter N. Cloning of the toxin gene from Pasteurella multocida and its role in atrophic rhinitis. J Gen Microbiol,1990,136(1):81-87
153. Lax A J, Pullinger G D, Baldwin M R. The Pasteurella multocida toxin interacts with signalling pathways to perturb cell growth and differentiation. Int J Med Microbiol,2004, 293(7-8):505-512
154. Leotta G A, Chinen I, Vigo G B, Pecoraro M, Rivas M. Outbreaks of avian cholera in Hope Bay, Antarctica. Journal of Wildlife Disease,2006,42:259-270
155. Liao C M, Huang C, Hsuan S L, Chen Z W, Lee W C, Liu C I, Winton J R, Chien M S. Immunogenicity and efficacy of three recombinant subunit Pasteurella multocida toxin vaccines against progressive atrophic rhinitis in pigs. Vaccine,2006,24(1):27-35
156. Lichtensteiger C A, Steenbergen S M, Lee R M. Direct PCR analysis toxigenic Pasteurella multocida. JClin Microbiol,1996,34(12):3035-3039
157. Lion C, Conroy M C, Carpentier A M, Lozniewski A. Antimicrobial susceptibilities of Pasteurella strains isolated from humans. Int JAntimicrob Agents,2006,27:290-293
158. Lugtenberg, B., Van Boxtel, R.& De Jong, M. Atrophic rhinitis in swine:correlation of Pasteurella multocida pathogenicity with membrane protein and lipopolysaccharide patterns, Infect Immun,1984,46(1):48-54
159. Luke D. Pasteurellosis in swine. Veterinary Record,1947,59:409-411
160. Luo Y, Glisson J R, Jackwood M W, Hancock R E, Bains M, Cheng I H, Wang C. Cloning and characterization of the major outer membrane protein gene (ompH) of Pasteurella multocida X-73.JBacteriol,1997,179:7856-7864
161. Luo Y, Zeng Q, Glisson J R, Jackwood M W, Cheng I H, Wang C. Sequence analysis of Pasteurella multocida major outer membrane protein (ompH) and application of synthetic peptides in vaccination of chickens against homologous strain challenge. Vaccine,1999,17: 821-831.
162. Lu Y S, Lai W C, Pakes S P, Nie L C. A monoclonal antibody against a Pasteurella multocida outer membrane protein protects rabbits and mice against Pasteurellosis. Infect Immun,1991, 59:172-180.
163. Marandi M V, Mittal K R. Role of outer membrane protein H (ompH)- and ompA-specific monoclonal antibodies from hybridoma tumors in protection of mice against Pasteurella multocida. Infect Immun,1997,65:4502-4508
164. Magnusson H. Bacterium viscosum equi (Adsersen) in suckling pigs and its relation to Bacillus polymorphus suis (Degen) in focal interstitial nephritis in swine. Proceedings of the 11 th International Veterinary Congress:Report for Section Meetings,1931,3:488-510
165. Magyar T, King V.L, Kovacs F. Evaluation of vaccines for atrophic rhinitis—a comparison of three challenge models. Vaccine,2002,20(13-14):1797-1802
166. Manning P J, DiGiacomo R F, DeLong D. Pasteurellosis in Laboratory Animals. In: Pasteurella and Pasteurellosis. Academic Press, London,1989,263-302
167. May B J, Zhang Q, Li L L, Paustian M L, Whittam T S, Kapur V. Complete genomic sequence of Pasteurella multocida, Pm70. Proc Natl Acad Sci USA,2001,98:3460-3465
168. McDermott P F, Zhao S, Wagner D D, Simjee S, Walker R D, White D G. The food safety perspective of antibiotic resistance. Animal Biotechnology,2002,13:71-84
169. Mendes S, Carmichael K P, Nunnally J C, Glisson J R, Cheng I H, Harmon B G. Lesions resulting from attempted Shwartzman reaction in turkey poults inoculated with Pasteurella multocida lipopolysaccharide. Avian Dis,1994,38:790-796
170. Merlin C, Gardiner G, Durand S, Masters M. The Escherichia coli metD locus encodes an ABC transporter which includes Abc(MetN), YaeE (MetI), and YaeC (MetQ). J Bacteriol, 2002,184:5513-5517
171. Mizan S, Henk A, Stallings A, Maier M, Lee M D. Cloning and characterization of sialidases with 2-6' and 2-3'sialyl lactose specificity from Pasteurella multocida. J Bacteriol,2000, 182:6874-6883.
172. Mooi F R, Jansen W H, Brunings H, Gielen H, van der Heide H G, Walvoort H C, Guinee P A. Construction and analysis of Bordetella pertussis mutants defective in the production of fimbriae. Microb Pathog,1992,12:127-135
173. Morrison R B, Pijoan C, Hilley H D, Rapp V. Microorganisms associated with pneumonia in slaughter weight swine. Canadian Journal of Comparative Medicine,1985,49:129-137
174. Mullan P B, Lax A J. Pasteurella multocida toxin is a mitogen for bone cells in primary culture. Infect Immun,1996,64(5):959-965
175. Murphy A C, Rozengurt E. Pasteurella multocida toxin selectively facilitates phosphatidylinositol 4,5-bisphosphate hydrolysis by bombesin, vasopressin, and endothelin Requirement for a functional G protein. JBiol Chem,1992,267:25296-25303
176. Murray P R., Baron E J, Jorgensen J H, Pfaller M A, Yolken R H. Manual of clinical microbiology,8th edition, American Society for Microbiology, Washington, D.C.2003
177. Musser J M. Molecular population genetic analysis of emerged bacterial pathogens:selected insights. Emerg Infect Dis,1996,2(1):1-17
178. Mutters R, Ihm P, Pohl S, Frederiksen W, Mannheim W. Reclassification of the genus Pasteurella Trevisan 1887 on the basis of deoxyribonucleic acid homology, with proposals for the new species Pasteurella dagmatis, Pasteurella canis, Pasteurella stomatis, Pasteurella anatis and Pasteurella langaa. International Journal of Systematic Bacteriology,1985,35: 309-322
179. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; approved standard—2nd edition. NCCLS document M31-A. National Committee for Clinical Laboratory Standards, Wayne, Pa.2002
180. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; informational supplement. NCCLS document M31-S1. National Committee for Clinical Laboratory Standards, Wayne, Pa.2004
181.Nagai S, Spmeno S, Yagihashi T. Differention of toxigenic Pasteurella multocida from nontoxigenic isolates of Pasteurella multocida by PCR. J Clin Microbiol,1994, 32(4):1004-1010.
182. Nakai T A, Swata M. Tsuji Y. Samejima, and K. Kume. Purification of dermonecrotic toxin from a sonic extract of Pasteurella multocida SP-72 serotype D. Infect Immun,1984, 46(3):429-434
183. Ogunnariwo J A, Schryvers A B. Characterization of a novel transferrin receptor in bovine strains of Pasteurella multocida. J Bacteriol,2001,183:890-896
184. Orth JH, Blocker D, Aktories K. His 1205 and His 1223 are essential for the activity of the mitogenic Pasteurella multocida toxin. Biochemistry,2003,42(17):4971-4977
185. Pabs-Garnon L F, Soltys M A. Multiplication of Pasteurella multocida in the spleen, liver and blood of turkeys inoculated intravenously. Can J Comp Med,1971,35:147-149
186. Pandit K K and Smith J E Capsular hyaluronic acid in Pasteurella multocida type A and its counterpart in type D. Res Vet Sci,1993,54:20-24
187. Petersen S K, Foged N T. Cloning and expression of Pasteurella multocida toxin gene, toxA, in Escherichia coli. Infect Immun,1989,57,3907-3913
188. Petersen S K. The complete nucleotide sequence of the Pasteurella multocida toxin gene and evidence for a transcriptional repressor, TxaR. Mol Microbiol,1990,4(2):821-830
189. Petersen S K, Foged N T, Bording A. Recombinant derivatives of Pasteurella multocida toxin: candidates for a vaccine against progressive atrophic rhinitis. Infect Immun,1991, 59(4):1387-1393
190. Pettit R K, Ackermann M R, Rimler R B. Receptor-mediated binding of Pasteurella multocida dermonecrotic toxin to canine osteosarcoma and monkey kidney (Vero) cells. Lab Invest,1993,69(2):94-100
191. Pijoan C and Ochoa G. Interaction between a hog cholera vaccine strain and Pasteurella multocida in the production of porcine pneumonia. Journal of Comparative Pathology, 1978,88:167-170
192. Pijoan C, Morrison R B, Hilley H D. Serotyping of Pasteurella multocida isolated from swine lungs collected at slaughter. J Clin Microbiol,1983,17:1074-1076
193. Pijoan C, Lastra A, Ramirez C, Leman AD. Isolation of toxigenic strains of Pasteurella multocida from lungs of pneumonic swine. Journal of the American Veterinary Medical Association,1984,185:522-523
194. Pijoan C. Pneumonic Pasteurellosis. In Diseases of Swine,9th edn. ed. Ames:Iowa University Press.2006
195. Pizza M, Covacci A, Bartoloni A, Perugini M, Nencioni L, De Magistris MT, et al. Mutants of pertussis toxin suitable for vaccine development. Science,1989,246(4929):497-500
196. Pruimboom I M, Rimler R B, Ackermann M R, Brogden K A. Capsular hyaluronic acid-mediated adhesion of Pasteurella multocida to turkey air sac macrophages. Avian Dis, 1996,40:887-893
197. Pullinger G D, Sowdhamini R, Lax A J. Localization of functional domains of the mitogenic toxin of Pasteurella multocida. Infect Immun,2001,69(12):7839-7850
198. Pullinger G D, Bevir T, Lax A J. The Pasteurella multocida toxin is encoded within a lysogenic bacteriophage. Mol Microbiol,2004,51:255-269
199. Raemdonck D L, Tanner A C, Tolling S T, Michener S L. Antimicrobial susceptibility of Actinobacillus pleuropneumoniae, Pasteurella multocida and Salmonella choleraesuis isolates from pigs. Veterinary Record,1994,134:5-7
200. Ramdani, Adler B. Opsonic monoclonal antibodies against lipopolysaccharide (LPS) antigens of Pasteurella multocida and the role of LPS in immunity. Vet Microbiol,1991,26:335-347
201. Ram S, Cox A D, Wright J C. Neisserial lipooligosaccharide is a target for complement component c4b. Inner core phosphoethanolamine residues define C4b linkage specificity. J Biol Chem,2003,278:50853-50862
202. Rasschaert G, Houf K, Imberechts H, Grijspeerdt K, De Zutter L, Heyndrickx M. Comparison of Five Repetitive-Sequence-Based PCR Typing Methods for Molecular Discrimination of Salmonella enterica Isolates. JClin Microbiol,2005,43(8):3615-3623
203. Rebers P A, Jensen A E, Laird G A. Expression of pili and capsule by the avian strain P-1059 of Pasteurella multocida. Avian Dis,1988,32:313-318
204. Rhoades K R, Rimler R B. Effects of Pasteurella multocida endotoxins on turkey poults. Avian Dis,1987,31:523-526
205. Rhoades K R, Rimler R B. Pasteurella multocida colonization and invasion in experimentally exposed turkey poults. Avian Dis,1990,34:381-383
206. Rhoades K R, Rimler R B. Effects of Pasteurella multocida endotoxins on turkey poults. Avian Dis,1987,31:523-526
207. Richard F R. Pasteurella multocida and its role in porcine pneumonia. Animal Health Research Reviews,2007,7(1/2):13-29
208. Rimler R B, Rhoades K R. Hyaluronidase and chondroitinase activity of Pasteurella multocida serotype B:2 involved in hemorrhagic septicaemia. Vet Rec,1994,134:67-68
209. Rimler R B. Purification of a cross-protective antigen from Pasteurella multocida grown in vitro and in vivo. Avian Dis,2001,45:572-580
210. Roberts E D, Switzer W P, L' Ecuyer C. Influence of Pasteurella multocida and Mycoplasma hyorhinis (PPLO) on the histopathology of field cases of swine pneumonia. Cornell Veterinarian,1962,52:306-327
211. Rosen M N. Diseases transmitted from animals to man. Thomas Pub Illinois,1975:129-138
212. Ruffolo C G, Tennent J M, Michalski W P, Adler B. Identification, purification, and characterization of the type 4 fimbriae of Pasteurella multocida. Infect Immun,1997,65: 339-343
213. Ruffolo C G, Jost B H, Adler B. Iron-regulated outer membrane proteins of Pasteurella multocida and their role in immunity. Vet Microbiol,1998,59:123-137
214. Rutter J M. Atrophic rhinitis in swine. Adv Vet Sci Comp Med,1985,29:239-279
215. Rutter J M, Luther P D. Cell culture assay for toxigenic Pasteurella multocida from atrophic rhinitis of pigs. Vet Rec,1984,114(2):393-396
216. Salmon S A, Watts J L, Case C A, Hoffman L J, Wegener H C, Yancey Jr R J. Comparison of MICs of ceftiofur and other antimicrobial agents against bacterial pathogens of swine from the United States, Canada, and Denmark. JClin Microbiol,1995,33:2435-2444
217. Scharmann W R, Drzeniek R, Blobel H. Neuraminidase of Pasteurella multocida. Infect Immun,1970,1:319-320
218. Schenkein H A, Barbour S E, Berry C R, Kipps B, Tew J G. Invasion of human vascular endothelial cells by Actinobacillus actinomycetemcomitans via the receptor for platelet-activating factor. Infect Immun,2000,68:5416-5419
219. Schofield F W, Ingle R T. Natural and experimental hemorrhagic septicemia in swine. Annual Report of the Ontario Veterinary College for 1940,1942,29:23-27
220. Scott J P. Swine influenza. Proceedings of the ⅩⅢth International Veterinary Congress,1938, 1:479-490
221. Selander R K, Beltran P, Smith N H, Helmuth R, Rubin F A, Kopecko D J, Ferris K, Tall B D, Cravioto A, Musser J M. Evolutionary genetic relationships of clones of Salmonella serovars that cause human typhoid and other enteric fevers. Infect Immun,1990,58(7):2262-2275
222. Serino L, Virji M. Genetic and functional analysis of the phosphorylcholine moiety of commensal Neisseria lipopolysaccharide. Mol Microbiol,2002,43:437-448
223. Shivachandra S B, Kumar A A, Chaudhuri P. Molecular characterization of avian strains of Pasteurella multocida serogroup-A:1 based on amplification of repetitive regions by PCR. Comp Immunol Microbiol Infect Dis.2008,31(1):47-62
224. Snipes K P, Hirsh D C. Association of complement sensitivity with virulence of Pasteurella multocida isolated from turkeys. Avian Dis,1986,30:500-504
225. Snipes K P, Ghazikhanian G Y, Hirsh D C. Fate of Pasteurella multocida in the blood vascular system of turkeys following intravenous inoculation:comparison of an encapsulated, virulent strain with its a virulent, a capsular variant. Avian Dis,1987,31:254-259.
226. Snipes K P, Hansen L M, Hirsh D C. lasma-and iron regulated expression of high molecular weight outer membrane proteins by Pasteurella multocida. Am J Vet Res,1988, P 49:1336-1338
227. Spray R S. The bacteria in normal and diseased lungs of swine. J Infect Dis.1922,31:10-21
228. Steenbergen S M, Lichtensteiger C A, Caughlan R, Garfinkle J, Fuller T E, Vimr E R. Sialic acid metabolism and systemic pasteurellosis. Infect Immun,2005,73:1284-1294
229. Staddon J M, Chanter N, Lax A J, Higgins T E, Rozengurt E. Pasteurella multicoda toxin, a potent mitogen, stimulates protein kinase C-dependent and -independent protein phosphorylation in Swiss 3T3 cells. JBiol Chem,1990,265(34):11841-11848
230. St Michael F, Li J, Cox A D. Structural analysis of the core oligosaccharide from Pasteurella multocida strain X73. Carbohydr Res,2005,340:1253-1257
231. Straus D C, Purdy C W. In vivo production of neuraminidase by Pasteurella haemolytica A1 in goats after transthoracic challenge. Infect Immun,1994,62:4675-4678
232. Straw B E, Dewey C E, Erickson E D. Interpreting culture reports from swine lungs. Swine Health and Production,1996,4:200-201
233. Tabatabai LB, Zehr E S. Identification of five outer membrane-associated proteins among cross-protective factor proteins of Pasteurella multocida. Infect Immun,2004,72:1195-1198
234. Tatum F M, Yersin A G, Briggs R E. Construction and virulence of a Pasteurella multocida fhaB2 mutant in turkeys. Microb Pathog,2005,39:9-17
235. To H, Someno S, Nagai S. Development of a genetically modified nontoxigenic Pasteurella multocida toxin as a candidate for use in vaccines against progressive atrophic rhinitis in pigs. Am J Vet Res,2005,66:113-118
236. Townsend K M, O'Boyle D, Phan T T, Hanh T X, Wijewardana T G, Wilkie I, Trung N T, Frost A J. Acute septicaemic pasteurellosis in Vietnamese pigs. Vet Microbiol,1998,63: 205-215
237. Townsend K M, Boyce J D, Chung J Y, Frost A J, Adler B. Genetic organization of Pasteurella multocida cap loci and development of a multiplex capsular PCR typing system. J Clin Microbiol,2001,39:924-929
238. Toyotsugu Nakai, Akira Sawata, Masayoshi, et al. Characterization of dermonecrotic toxin produced by serotype D strains of Pasteurella multocida. Am J Vet Res,1984,45(11): 2410-2413
239. Truscott W M, Hirsh D C. Demonstration of an outer membrane protein with antiphagocytic activity from Pasteurella multocida of avian origin. Infect Immun,1988,56:1538-1544
240. Tsuji M, Matsumoto M. Pathogenesis of fowl cholera:influence of encapsulation on the fate of Pasteurella multocida after intravenous inoculation into turkeys. Avian Dis,1989, 33:238-247.
241.Vasfi Marandi M, Mittal K R. Role of outer membrane protein H (OmpH)-and OmpA-specific monoclonal antibodies from hybridoma tumors in protection of mice against Pasteurella multocida. Infect Immun,1997,65:4502-4508
242. Vecht U, Wisselink H J, van Dijk J E, Smith H E. Virulence of Streptococcus suis type 2 strains in newborn germfree pigs depends on phenotype. Infect Immun,1992,60:550-556
243. Veken J W, Oudega B, Luirink J, De Graaf F K. Binding of bovine transferrin by Pasteurella multocida serotype B:2,5, a strain which causes haemorrhagic septicaemia in buffalo and cattle. Microb Lett,1994,115:253-258
244. Vera Lizarazo Y A, Rodn'guez Ferri E F, Martin de la Fuente A J, Gutie'rrez Martin C B. Evaluation of changes in antimicrobial susceptibility patterns of Pasteurella multocida subsp multocida isolates from pigs in Spain in 1987-1988 and 2003-2004. American Journal of Veterinary Research,2006,67:663-668
245. Verma N D. Pasteurella multocida B:2 in haemorrhagic septicemia outbreak in pigs in India. Veterinary Record,1988,123:63
246. Walsh C, Fanning S. Antimicrobial resistance in foodborne pathogens--a cause for concern? Curr Drug Targets,2008,9:808-815
247. Ward P N, Miles A J, Sumner I G., Thomas L H, Lax A J. Activity of the Mitogenic Pasteurella multocida Toxin Requires an Essential C-Terminal Residue Infect Immun, 1998,66(12):5636-5642
248. White D G, Zhao S, Simjee S, Wagner D D, McDermott P F. Antimicrobial resistance of foodborne pathogens. Microbes Infect,2002,4:405-412
249. White D J, Jolley W L, Purdy C W, Straus D C. Extracellular neuraminidase production by a Pasteurella multocida A-3 strain associated with bovine pneumonia. Infect Immun,1995, 63:1703-1709
250. Wilson B A, Zhu X, Ho M, Lu L. Pasteurella multocida toxin activates the inositol triphosphate signaling pathway in Xenopus oocytes via G(q)alpha-coupled phospholipase C-betal. JBiol Chem, (1997)272:1268-1275
251. Wijewardana T G, Sutherland A D. Bactericidal activity in the sera of mice vaccinated with Pasteurella multocida type A. Vet Microbiol,1990,24:55-62
252. Williams K J, Halkes K M, Kamerling J P, DeAngelis P L. Critical elements of oligosaccharide acceptor substrates for the Pasteurella multocida hyaluronan synthase. JBiol Chem,2006,281:5391-5397
253. Wozniak D J, Hsu L Y, Galloway D R. His-426 of the Pseudomonas aeruginosa exotoxin A is required for ADP-ribosylation of elongation factor II. Proc Natl Acad Sci USA,1988,85(23): 8880-8884
254. Yamamoto J, Sakano T, Shimizu M. Drug resistance and R plasmids in Pasteurella multocida isolates from swine. Microbiology and Immunology,1990,34:715-721
255. Yoshimura H, Ishimaru M, Endoh Y S, Kojima A. Antimicrobial susceptibility of Pasteurella multocida isolated from cattle and pigs. J Vet Med B,2001,48:555-560
256. Yu H, Chokhawala H, Karpel R, Wu B, Zhang J, Zhang Y, Jia Q, Chen X. A multifunctional Pasteurella multocida sialyltransferase:a powerful tool for the synthesis of sialoside libraries. J Am Chem Soc,2005,127:17618-17619
2. 白新盛. 畜禽重大疫病生物技术防制研究.北京：中国农业科技出版社,1998
3. 陈焕春.规模化猪场疫病控制与净化.北京：中国农业出版社,2000：260-265
4. 常丙功,李红,石朝辉,张丽芳,刘星,张远富.用随意扩增多态性DNAPCR方法检查实验小鼠的嗜肺性巴氏杆菌.中华微生物学和免疫学杂志,2001,21(6)：694
5. 崔尚金.猪传染性萎缩性鼻炎流行特点、危害状况、诊断与防治净化.猪业科学,2009,6：22-28
6. 戴自英.临床抗菌药物学.北京：人民卫生出版社,1985
7. 东秀珠,蔡妙英.常见细菌系统鉴定手册.北京：科学出版社,2001,9-348
8. F.奥斯伯,R.布伦特,R.E.金斯顿,等著.精编分子生物学实验指南.北京：科学出版社,1998,366-370
9. 范玉霞.猪萎缩性鼻炎的防治对策.动物医学进展,2006,25(5)：114-116
10.甘肃农业大学主编.兽医微生物学实验指导.北京：农业出版社,1980：1-31
11.国际兽疫局编著.诊断试剂和疫苗标准手册.青岛新闻出版局,1996.
12.管宇,沈志强,刘吉山,庞万勇,王燕,莫玲.应用16S rRNA基因测序法鉴定禽多杀性巴氏杆菌的研究.中国预防兽医学报,2003,25(5)：349-352
13.黄显会,陈杖榴,张淑婷,曾振灵.禽多杀性巴氏杆菌感染对麻保沙星在鸡体内药动学特征的影响研究.畜牧兽医学报,2003,34(1)：98-102
14.纪剑飞,张成刚.包涵体重组蛋白的纯化及复性.沈阳药科大学学报,1998,15(4)：303-307
]5.金天明, 高丰,佟庆彬,武迎红.巴氏杆菌对链霉素和磺胺耐药机制的研究.畜牧与兽医,2007,39(3)：5-7
16.金天明,武迎红,李向阳,刘海学,王学理,冯海华,高丰.巴氏杆菌耐药性检测芯片的研制.畜牧与兽医,2008,40(9)：74-75
17.刘杰,杨建德,刘文周,孔宪刚.猪萎缩性鼻炎研究进展.中国兽医杂志,2003,39(11)：30-32
18.刘杰,杨建德,孔宪刚,刘文周.多杀巴氏杆菌毒素的研究进展.畜牧兽医科技信息,2002,2(05)：17-20
19.刘建杰,吴斌,陈焕春.猪萎缩性鼻炎产毒多杀性巴氏杆菌的研究进展.动物医学进展,2002,23(1)：10-13
20.卢圣栋主编.现代分子生物学实验技术.第二版,北京：中国协和医科大学出版社,1999
21.鲁承,金鑫,杨咏洁.多重PCR在猪传染性萎缩性鼻炎诊断中的应用.中国兽医科技,2003,39(12)：7-9
22.陆承平.兽医微生物学(第三版).北京：中国农业出版社,2001：249-254
23.李雪,金莉莉,王秋.病原微生物分子分型技术研究进展.中国公共卫生,2007,23(3)：373-374
24.马俊英,刘健华,陈杖榴,曾振灵.细菌分型的分子生物学技术研究进展.中国兽医科学,2007,37(10)：914-918
25.倪语星,洪秀华.细菌耐药性监测与抗感染治疗.北京：人民军医出版社,2002
26.萨姆布鲁克J,弗里奇E F,曼尼阿蒂斯T著,金冬雁,黎孟枫等译.分子克隆实验指南(第二版).北京：科学出版社,1996
27.沈关心,周汝麟主编.现代免疫学实验技术.武汉:湖北科学技术出版社,1998,112-119
28.斯特劳.B.E,阿莱尔.S.D,蒙加林.W.L,泰勤.D.J主编.猪病学(第八版).赵德民,张中秋,沈建忠主译,狄伯雄,甘孟侯主校.北京：中国农业大学出版社,2000
29.汤锦如,阮宪章,汪辰生等,猪传染性萎缩性鼻炎诊断研究报告.中国兽医杂志,1981,7(9)：9-11
30.唐先春,吴斌,陈焕春等.猪产毒多杀性巴氏杆菌研究进展.动物医学进展,2003,10(5)：14-17
31.唐先春,吴斌,陈焕春等.猪多杀性巴氏杆菌PCR诊断方法的建立与应用.中国兽医科技,2004,2(2)：46-48
32.唐先春,吴斌,刘国平等.应用双重PCR检测产毒素多杀性巴氏杆菌.中国兽医学报,2005,25(4)：374-375
33.汪家政,范明.蛋白质技术手册.北京：科学出版社,2000
34.魏洁.检测产毒多杀性巴氏杆菌毒素抗体乳胶凝集试验方法的研究.[硕士学位论文].武汉：华中农业大学图书馆,2005
35.吴斌,陈焕春,何启盖.应用乳胶凝集实验进行猪传染性萎缩性鼻炎血清流行病学调查.中国兽医科技,2001,31(6)：21-22
36.吴斌,唐先春,陈焕春,王大鹏.猪源多杀性巴氏杆菌ompH基因的克隆、表达.畜牧兽医学报,2005,36(7)：701-704
37.吴范庚.我国多杀性巴氏杆菌血清学鉴定及交互免疫试验.中国兽医杂志,1997,23(8)：14-15
38.王大鹏,吴斌,周锐等.猪源D型产毒素多杀性巴氏杆菌toxA基因的克隆与表达.中国兽医学报,2006,26(3)：271-273
39.杨留战,苑士祥,张树成等.产毒多杀性巴氏杆菌和支气管败血波氏杆菌在猪萎缩性鼻炎中的流行病学研究.中国兽医科技,1992,7(22)：3-5
40. Aarestrup F M. Association between the consumption of antimicrobial agents in animal husbandry and the occurrence of resistant bacteria among food animals. Int J Antimicrob Agents,1999,12,279-285
41. Aarestrup F M, Seyfarth A M, Angen 0. Antimicrobial susceptibility of Haemophilus parasuis and Histophilus somni from pigs and cattle in Denmark. Vet Microbiol,2004,101: 143-146
42. Abdoulaye BN. Manual of diagnostic tests and vaccines for terrestrial animals,5th edition, NY:the OIE International Committee,2004
43. Adler B, Bulach D, Chung J, Doughty S, Hunt M, Rajakumar K, Serrano M, van Zanden A, Zhang Y, Ruffolo C. Candidate vaccine antigens and genes in Pasteurella multocida. J. Biotechnol,1999,73:83-90
44. Al-haj Ali H, Sawada T, Hatakeyama H, Katayama Y, Ohtsuki N, Itoh O. Invasion of chicken embryo fibroblast cells by avian Pasteurella multocida. Vet Microbiol,2004,104:55-62
45. Amigot J A, Torremorell M, Pijoan C. Evaluation of techniques for the detection of toxigenic Pasteurella multocida strain from pigs. J Vet Diagn Invest,1998,10(2): 169-173.
46. Amonsin A, Wellehan J F, Li L L, Laber J, Kapur V. DNA fingerprinting of Pasteurella multocida recovered from avian sources. JClin Microbiol.2002,40(8):3025-3031
47. Arashima Y, Kumasaka K. Pasteurellosis as zoonosis. Intern Med,2005,44:692-693
48. Backstrom L R, Brim T A, Collins M T. Development of turbinate lesions and nasal colonization of Bordetella bronchiseptica and Pasteurella multocida during long term exposure of healthy pigs affected by atrophic rhinitis. Can J Vet Res,1988,52:23-29
49. Baekbo P. Pathogenic properties of Pasteurella multocida in the lungs of pigs; the significance of toxin production. Proceedings of the International Pig Veterinary Society, 1988,10:58
50. Bagley K C, Abdelwahab S F, Tuskan RG. Pasteurella multocida toxin activates human monocyte-derived and murine bone marrow-derived dendritic cells in vitro but suppresses antibody production in vivo. Infect Immun,2005,73(1):413-421
51. Baldwin M R, Lakey J H, Lax A J. Identification and characterization of the Pasteurella multocida toxin translocation domain. Mol Microbiol,2004,54(1):239-250
52. Bethe A, Wieler LH, Selbitz HJ, Ewers C. Genetic diversity of porcine Pasteurella multocida strains from the respiratory tract of healthy and diseased swine. Vet Microbiol,2009, 139(1-2):97-105
53. Blackall P J, Pahoff J L, Bowles R. Phenotypic characterisation of Pasteurella multocida isolates from Australian pigs.Vet microbiol,1997,57(4):355-360
54. Blackall P J, Miflin J K. Identification and typing of Pasteurella multocida:a review. Avian Pathol,2000,29(4):271-87
55. Bosch M, Garrido E, Llagostera M, de Rozas A M P, Badiola I, Barbe J. Pasteurella multocida exbB, exbD and tonB genes are physically linked but independently transcribed. FEMS Microbiol Lett,2002,210:201-208
56. Borrathybay E, Sawada T, Kataoka Y, Ohtsu N, Takagi M, Nakamura S, Kawamoto E A 39 kDa protein mediates adhesion of avian Pasteurella multocida to chicken embryo fibroblast cells. Vet Microbiol,2003,97:229-243
57. Bousquet E, Morvan H, Aitken I, Morgan J H. Comparative in vitro activity of doxycycline and oxytetracycline against porcine respiratory pathogens. Veterinary Record,1997,141: 37-40
58. Boyce J D, Adler B. The capsule is a virulence determinant in the pathogenesis of Pasteurella multocida M1404(B:2). Infect Immun,2000,68:3463-3468
59. Boyce J D, Chung J Y, Adler B. Pasteurella multocida capsule:composition, function and genetics. JBiotechnol,2000,83:153-160
60. Boyce J D, Cullen P A, Nguyen V, Wilkie I, Adler B. Analysis of the Pasteurella multocida outer membrane subproteome and its response to the in vivo environment of the natural host. Proteomics,2006,6:870-880
61. Bowersock T L, Hooper T, Pottenger R. Use of ELISA to detect toxigenic Pasteurella multocida in atrophic rhinitis in swine. J Vet Diagn Invest,1992,4(3):419-422
62. Bowles R E, Pahoff J L, Smith B N, Blackall P J. Ribotype diversity of porcine Pasteurella multocida from Australia. Aust Vet J.2000,78(9):630-635
63. Brockmeier S L, Register K B. Effect of temperature modulation and bvg mutation of Bordetella bronchiseptica on adhesion, intracellular survival and cytotoxicity for swine alveolar macrophages. Vet Microbiol,2000,73:1-12
64. Brockmeier S L, Palmer M V, Bolin S R, Rimler R B. Effects of intranasal inoculation with Bordetella bronchiseptica, porcine reproductive and respiratory syndrome virus, or a combination of both organisms on subsequent infection with Pasteurella multocida in pigs. American Journal of Veterinary Research,2001,62:521-525
65. Brockmeier S L, Halbur P G, Thacker E L. Porcine respiratory disease complex. In:Borgden KA, Guthmiller JM, editors. Polymicrobial diseases. Washington, DC:ASM,2002.
66. Brockmeier S L. Prior infection with Bordetella bronchiseptica increases nasal colonization by Haemophilus parasuis in swine. Vet Microbiol.2004,99(1):75-78
67. Bronzwaer S L, Cars O, Buchholz U, Molstad S, Goettsch W, Veldhuijzen I K, Kool J L, Sprenger M J, Degener J E. A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerg Infect Dis,2002,8:278-282
68. Brogden K A, Nordholm G, Ackermann M. Antimicrobial activity of cathelicidins BMAP28, SMAP28, SMAP29, and PMAP23 against Pasteurella multocida is more broad-spectrum than host species specific. Vet Microbio,2007,119:76-81
69. Cai X, Chen H, Blackall P J, Yin Z, Wang L, Liu Z, Jin M. Serological characterization of Haemophilus parasuis isolates from China. Vet Microbiol,2005,111:231-236
70. Carvalho LFOS, Segales J, Pijoan C. Effect of porcine reproductive and respiratory syndrome virus on subsequent Pasteurella multocida challenge in pigs. Vet Microbiol,1997, 55:241-246
71. Casarez E A, Pillai S D, Mott J B, Vargas M, Dean K E, Di Giovanni G D. Direct comparison of four bacterial source tracking methods and use of composite data sets. J Appl Microbiol, 2007,103(2):350-364
72. Caprioli A, Busani L, Martel J L, Helmuth R. Monitoring of antibiotic resistance in bacteria of animal origin:epidemiological and microbiological methodologies. Int J Antimicrob Agents,2000,14:295-301
73. Carter G R. Studies on Pasteurella multocida I. A haemagglutination test for the identification of serological types. Am J Vet Res,1955,16:481-484
74. Carter GR. Pasteurellosis:Pasteurella multocida and Pasteurella haemolytica. Adv Vet Sci, 1967,11:321-379
75. Carter G R, Chengappa M M. Hyaluronidase production by type B Pasteurella multocida from cases of hemorrhagic septicemia. J Clin Microbiol,1980,11:94-96
76. Chandrasekaran S, Yeap P C. Pasteurella multocida in pigs:The serotypes and the assessment of their virulence in mice. Br Vet J,1982,138:332-336
77. Chang W H, Carter G R. Multiple drug resistance in Pasteurella multocida and Pasteurella haemolytica from cattle and swine. Journal of the American Veterinary Medical Association, 1976,169:710-712
78. Chansiripornchai N, Ramasoota P, Sasipreeyajan J, Svenson S B. Differentiation of avian pathogenic Escherichia coli (APEC) strains by random amplified polymorphic DNA (RAPD) analysis. Vet Microbiol,2001,80(1):75-83
79. Chanter N, Rutter J M, Luther P D. Rapid detection of toxigenic Pasteurella multocida by an agar overlay method. Vet Rec,1986,119(3):629-630
80. Chanter N, Rutter JM. Pasteurellosis in pigs and the determinants of cirulence of toxigenic Pasteurella multocida. London:Academic Press,1989.
81. Chanter N, Magyar T, Rutter JM. Interactions between Bordetella bronchiseptica and toxigenic Pasteurella multocida in atrophic rhinitis of pigs. Res Vet Sci,1989,47(1):48-53
82. Chih-Ming Liao, Chienjin Huang,Shih-Ling Hsuan. Immunogeniciti and efficacy of three recombinant subunit Pasteurella multocida. toxin vaccines against progressive atrophic rhinitis in pigs. Vaccine,2006; 24(2):27-35
83. Choi C, Chae C. Enhanced Detection of Toxigenic Pasteurella multocida Directly from Nasal Swabs Using a Nested Polymerase Chain Reaction. Vet J,2001,162(6):255-258
84. Choi C, Kim B, Cho W S, Kim J, Kwon D, Cheon D S, Chae C. Capsular serotype, toxA gene, and antimicrobial susceptibility profiles of Pasteurella multocida isolated from pigs with pneumonia in Korea. Veterinary Record,2001,149:210-212
85. Choi-Kim K, Maheswaran S K, Felice L J, Molitor T. W. Relationship between the iron regulated outer membrane proteins and the outer membrane proteins of in vivo grown Pasteurella multocida. Vet Microbiol,1991,28:75-92
86. Chung J Y, Wilkie I,Boyce J D, Townsend K M, Frost A J, Ghoddusi M, Adler B. Role of capsule in the pathogenesis of fowl cholera caused by Pasteurella multocida serogroup A. Infect Immun,2001,69:2487-2492
87. Chung J Y, Wilkie I, Boyce J D, Adler B. Vaccination against fowl cholera with acapsular Pasteurella multocida A:1.Vaccine,2005,23:2751-2755
88. Ciprian A, Pijoan C, Cruz T, Camacho J, Totora J, Colmenares G, Lopez-Revilla R and de la Garza M. Mycoplasma hyopneumoniae increases the susceptibility of pigs to experimental Pasteurella multocida pneumonia. Canadian Journal of Veterinary Research,1988,52: 434-438
89. Cote S, Harel J, Higgins R, Jacques M. Resistance to antimicrobial agents and prevalence of R plasmids in Pasteurella multocida from swine. American Journal of Veterinary Research, 1991,52:1563-1567
90. Cowart R P, Backstrom L, Brim T A. Pasteurella multocida and Bordetella bronchiseptica in atrophic rhinitis and pneumonia in swine. Can J Vet Res,1989,53(2):295-300
91. Cundell D R, Gerard N P, Gerard C, Idanpaan-Heikkila I, Tuomanen E I. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature,1995,377:435-438
92. Dabo S M, Confer A W, Quijano-Blas R A. Molecular and immunological characterization of Pasteurella multocida serotype A:3 OmpA:evidence of its role in P. multocida interaction with extracellular matrix molecules. Microb Pathog.2003,35:147-157
93. Dabo S M, Confer A W, Hartson S D. Adherence of Pasteurella multocida to fibronectin. Vet Microbiol,2005,110:265-275
94. Davies R L, MacCorquodale R, Baillie S, Caffrey B. Characterization and comparison of Pasteurella multocida strains associated with porcine pneumonia and atrophic rhinitis. J Med Microbiol,2003,52:59-67
95. Davies R L, MacCorquodale R, Reilly S. Characterisation of bovine strains of Pasteurella multocida and comparison with isolates of avian, ovine and porcine origin. Vet Microbiol, 2004,99:145-158
96. DeAngelis P L. Enzymological characterization of the Pasteurella multocida hyaluronic acid synthase. Biochemistry,1996,35:9768-9771
97. DeAngelis P L and Padgett-McCue A J. Identification and molecular cloning of a chondroitin synthase from Pasteurella multocida type F.JBiol Chem,2000,275:24124-24129
98. DeAngelis P L, White C L. Identification and molecular cloning of a heparosan synthase from Pasteurella multocida type D. JBiol Chem,2002,277:7209-7213
99. DeAngelis P L, White C L. Identification of a distinct, cryptic heparosan synthase from Pasteurella multocida types A, D, and F. J Bacteriol,2004,186:8529-8532
100. Diwan N, Bhagwat A A, Bauchan G B, Cregan P B. Simple sequence repeat DNA markers in alfalfa and perennial and annual Medicago species. Genome,1997,40(6):887-895
101. Djordjevic S P, Eamens G J, Ha H, Walker M J, Chin J C. Demonstration that Australian Pasteurella multocida isolates from sporadic outbreaks of porcine pneumonia are non-toxigenic (toxA-) and display heterogeneous DNA restriction endonuclease profiles compared with toxigenic isolates from herds with progressive atrophic rhinitis. J Med Microbiol,1998,47:679-688
102. Dominick M A, Rimler RB. Turbinate atrophy in gnotobiotic pigs intranasally inoculated with protein toxin isolated from type D Pasteurella multocida. J Vet Res,1986,47(7): 1532-1536
103. Dominick M A, Rimler R B. Turbinate osteoporosis in pigs following intranasal inoculation of purified Pasteurella toxin:histomorphometric and ultrastructural studies. Vet Pathol,1988, 25(1):17-27
104. Doughty S W, Ruffolo C G, Adler B. The type 4 fimbrial subunit gene of Pasteurella multocida. Vet Microbiol,2000,72:79-90
105. Drzeniek R, Scharmann W, Balke E. Neuraminidase and N-acetylneuraminate pyruvate-lyase of Pasteurella multocida. JGen Microbiol,1972,72:357-368
106. Dugal F, Belange M, Jacques M. Enhanced adherence of Pasteurella multocida to porcine tracheal rings preinfected with Bordetella bronchiseptica. Can J Vet Res,1992,56:260-264
107. Dziva F, Muhairwa A P, Bisgaard M, Christensen H. Diagnostic and typing options for investigating diseases associated with Pasteurella multocida, Vet Microbiol,2008,128:1-22
108. Elias B, Kruger M, P Gergely, R Voets, and P Rafai. Interaction between immunity to Bordetella bronchiseptica and infection of pig herds by Bordetella bronchiseptica and Pasteurella multocida. J Vet Med Sci,1996,55(2):617-622
109. Ewers C, Lubke-Becker A, Bethe A, Kiebling S, Filter M, Wieler L H. Virulence genotype of Pasteurella multocida strains isolated from different hosts with various disease status. Vet Microbiol,2006,114:304-317
110. Fernandez de Henestrosa A R, Badiola I, Saco M, Perez de Rozas A M, Campoy S, Barbe J. Importance of the galE gene on the virulence of Pasteurella multocida. FEMS Microbiol Lett, 1997,154:311-316
111. Finco-Kent D L, Galvin J E, Suiter B T. Pasteuella multocida toxin type D serological assay as an alternative to the toxin neutralization lethality test in mice. Biologicals,2001,29,7-10
112. Foged N T, Nielsen J P, Pederson K B. Differention of toxigenic Pasteurella multocida from nontoxigenic isolates of Pasteurella multocida by Enzyme-linked Immunosorbent Assay. J Clin Microbiol,1988,26(7):1419-1420
113. Foged N T, Nielsen J P, Jorsal S. Protection against progressive atrophic rhinitis by vaccination with Pasteurella multocida toxin purified by monoclonal antibodies. Vet Rec, 1989,125(1):7-11
114. Frank G H. Pasteurellosis of Cattle. In:Pasteurella and Pasteurellosis, Academic Press Limited, London.1989
115. Fuentes M and Pijoan C. Pneumonia in pigs induced by intranasal challenge exposure with pseudorabies virus and Pasteurella multocida. American Journal of Veterinary Research, 1987,48:1446-1448
116. Fuller TE, Kennedy M J, Lowery D E. Identification of Pasteurella multocida virulence genes in a septicemic mouse model using signature-tagged mutagenesis. Microb Pathog, 2000,29:25-38
117. Fussing V, Nielsen J P, Bisgaard M, Meyling A. Development of a typing system for epidemiological studies of porcine toxin-producing Pasteurella multocida ssp. multocida in Denmark. Vet Microbiol,1999,65(1):61-74
118. Galdiero M, Folgore A, Nuzzo I, Galdiero E. Neutrophil adhesion and transmigration through bovine endothelial cells in vitro by protein H and LPS of Pasteurella multocida. Immunobiology,2000,202:226-238
119. Gamage L N A, Wijewardana T G, Bastiansz H L G and Vipulasiri A A. An outbreak of acute pasteurellosis in swine caused by serotype B:2 in Sri Lanka. Sri Lanka Veterinary Journal, 1995,42:15-19
120. Gilmour N J L. Pasteurellosis in sheep. Vet Rec,1978,102:100-102
121. Glisson J R,Contreras M D, Cheng I H N, Wang C. Crossprotection studies with Pasteurella multocida bacterins prepared from bacteria propagated in iron-depleted medium. Avian Dis, 1993,37:1074-1079
122. Glorioso J C, Jones G W, Rush H G, Pentler L J, Darif C A, Coward J E. Adhesion of type A Pasteurella multocida to rabbit pharyngeal cells and its possible role in rabbit respiratory tract infections. Infect Immun,1982,35:1103-1109
123. Gois M, Sisak F, Kuksa F, Sovadina M. Incidence and evaluation of the microbial flora in the lungs of pigs with enzootic pneumonia. Zentralblatt fur Veterinarmedizin,1975,22: 205-219.
124. Gray-Owen S D, Schryvers A B. Bacterial transferrin and lactoferrin receptors. Trends Microbiol,1996,4:185-191
125. Gutierrez Martin C B, Rodriguez Ferri E F. In vitro susceptibility of Pasteurella multocida subspecies multocida strains isolated from swine to 42 antimicrobial agents. Zbl Bakt,1993, 279:387-393
126. Halbur P, Opriessnig T, Yaeger M, Yoon K-J. Case trends at the Iowa State University Veterinary Diagnostic Laboratory (ISU-VDL). Proceedings of Alpharma Technical Meeting on Swine Diseases, St. Hyacinth, Quebec and London, Ontario,2006,20-21
127. Hansen L M, Blanchard P C, Hirsh D C. Distribution of tet(H) among Pasteurella isolates from the United States and Canada. Antimicrobial Agents and Chemotherapy,1996,40: 1558-1560
128. Harmon B G, Glisson J R, Latimer K S, Steffens W L, Nunnally J C. Resistance of Pasteurella multocida A:3,4 to phagocytosis by turkey macrophages and heterophils. Am J Vet Res,1991,52:1507-1511
129. Harper M, Boyce J D, Wilkie I W, Adler B. Signaturetagged mutagenesis of Pasteurella multocida identifies mutants displaying differential virulence characteristics in mice and chickens. Infect Immun,2003,71:5440-5446
130. Harper M, Cox A D, St Michael F, Wilkie I W, Boyce J D, Adler B. A heptosyltransferase mutant of Pasteurella multocida produces a truncated lipopolysaccharide structure and is attenuated in virulence. Infect Immun,2004,72:3436-3443
131. Harper M, Boyce J D, Adler B. Pasteurella multocida pathogenesis:125 years after Pasteur. FEMS Microbiol Lett,2006,265:1-10
132. Heddleston K L, Watko L P, Rebers P A. Dissociation of a fowl cholera strain of Pasteurella multocida. Avian Dis,1964,8:649-657
133. Heddleston K L, Gallagher J E, Rebers P A. Fowl cholera:gel diffusion precipitin test for serotyping Pasteurella multocida from avian species. Avian Dis,1972,16:925-936
134.Hoskins IC, Thomas L H, Lax A J. Nasal infection with Pasteurella multocida causes proliferation of bladder epithelium in gnotobiotic pigs. Vet Rec,1997,140,22
135. Hunt M L, Adler B, Townsend K M. The molecular biology of Pasteurella multocida. Vet Microbiol,2000,72:3-25
136. Hunt M L, Boucher D J, Boyce J D, Adler B. In vivo-expressed genes of Pasteurella multocida. Infect Immun,2001,69:3004-3012
137. Hueppe F I. Ueber die Wildseuche und ihre Bedeutung fu"r die Nationalo konomie und die Hygiene.Berliner Klinische Wochenschrift,1886,44 (11):753-758
138. Inzana, T J, Todd, J, Ma J, Veit H. Characterisation of a non-hemolytic mutant of an Actinobacillus pleuropneumoniae serotype 5:role of 110 kDa hemolysin in virulence and immunoprotection. Microb Pathog,1991,10:281-296
139. Isaacson R E, Trigo E. Pili of Pasteurella multocida of porcine origin. FEMS Microbiol Lett, 1995,132:247-251
140. Jamaludin R, Blackall P J, Hansen M F, Humphrey S, Styles M. Phenotypic and genotypic characterisation of Pasteurella multocida isolated from pigs at slaughter in New Zealand. N Z Vet J,2005,53:203-207
141. Johnson R B, Dawkins H J S, Spencer T L. Electrophoretic profiles of Pasteurella multocida isolates from animals with haemorrhagic septicaemia. Am J Vet Res,1991,52:1644-1648
142. Jordan D, Hoffman L, Thacker E. Pasteurella multocida as a component of porcine respiratory disease complex (PRDC). Proceedings of the American Association of Swine Practitioners,2006,149-152
143. Jordan R W, Hamilton T D, Hayes C M. Modulation of the humoral immune response of swine and mice mediated by toxigenic Pasteurella multocida. FEMS Immunol Med Microbiol, 2003,39(1):51-59
144. Kachlany S C, Planet P J,DeSalle R, Fine D H, Figurski D H, Kaplan J B. Flp-1, the first representative of a new pilin gene subfamily, is required for non-specific adherence of Actinobacillus actinomycetemcomitans. Mol Microbiol,2001,40:542-554
145. Kamp E M, Bokken G C, Vermeulen T M. A specific and sensitive PCR assay suitable for large scale detection of toxigenic Pasteurella multocida in nasal and tonsillar swabs specimes of pigs. J Vet Diagn Invest,1996,8(1):304-309
146. Kehrenberg C, Schulze-Tanzil G, Martel J L, Chaslus-Dancla E, Schwarz S. Antimicrobial resistance in pasteurella and mannheimia:epidemiology and genetic basis. Vet Res,2001,32: 323-339
147. Kehrenberg C, Mumme J, Wallmann J, Verspohl J, Tegeler R, Kuhn T, Schwarz SMonitoring of florfenicol susceptibility among bovine and porcine respiratory tract pathogens collected in Germany during the years 2002 and 2003. Journal of Antimicrobial Chemotherapy,2004, 54:572-574
148. Kehrenberg C and Schwarz S. Plasmid-borne florfenicol resistance in Pasteurella multocida. Journal of Antimicrobial Chemotherapy,2005,55:773-775
149. Kengo Kitadokoro, Shigeki Kamitani, Aya Fukui, Hiromi Toshima,Masami Miyake, Yasuhiko Horiguchi. Structure and function of C-terminal catalytic region of Pasteurella multocida toxin. BMC Proceedings,2007,104(12):5139-5144
150. Killgore G, Thompson A, Johnson S, Brazier J, Kuijper E, Pepin J, Frost E H, Savelkoul P, Nicholson B, van den Berg R J, Kato H, Sambol S P, Zukowski W, Woods C, Limbago B, Gerding D N, McDonald L C. Comparison of seven techniques for typing international epidemic strains of Clostridium difficile:restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing. JClin Microbiol,2008,46(2):431-437
151. Kimura A, Mountzouros K T, Relman D A, Falkow S, Cowell J L. Bordetella pertussis filamentous hemagglutinin:evaluation as a protective antigen and colonization factor in a mouse respiratory infection model. Infect Immun,1990,58:7-16
152. Lax A J, Chanter N. Cloning of the toxin gene from Pasteurella multocida and its role in atrophic rhinitis. J Gen Microbiol,1990,136(1):81-87
153. Lax A J, Pullinger G D, Baldwin M R. The Pasteurella multocida toxin interacts with signalling pathways to perturb cell growth and differentiation. Int J Med Microbiol,2004, 293(7-8):505-512
154. Leotta G A, Chinen I, Vigo G B, Pecoraro M, Rivas M. Outbreaks of avian cholera in Hope Bay, Antarctica. Journal of Wildlife Disease,2006,42:259-270
155. Liao C M, Huang C, Hsuan S L, Chen Z W, Lee W C, Liu C I, Winton J R, Chien M S. Immunogenicity and efficacy of three recombinant subunit Pasteurella multocida toxin vaccines against progressive atrophic rhinitis in pigs. Vaccine,2006,24(1):27-35
156. Lichtensteiger C A, Steenbergen S M, Lee R M. Direct PCR analysis toxigenic Pasteurella multocida. JClin Microbiol,1996,34(12):3035-3039
157. Lion C, Conroy M C, Carpentier A M, Lozniewski A. Antimicrobial susceptibilities of Pasteurella strains isolated from humans. Int JAntimicrob Agents,2006,27:290-293
158. Lugtenberg, B., Van Boxtel, R.& De Jong, M. Atrophic rhinitis in swine:correlation of Pasteurella multocida pathogenicity with membrane protein and lipopolysaccharide patterns, Infect Immun,1984,46(1):48-54
159. Luke D. Pasteurellosis in swine. Veterinary Record,1947,59:409-411
160. Luo Y, Glisson J R, Jackwood M W, Hancock R E, Bains M, Cheng I H, Wang C. Cloning and characterization of the major outer membrane protein gene (ompH) of Pasteurella multocida X-73.JBacteriol,1997,179:7856-7864
161. Luo Y, Zeng Q, Glisson J R, Jackwood M W, Cheng I H, Wang C. Sequence analysis of Pasteurella multocida major outer membrane protein (ompH) and application of synthetic peptides in vaccination of chickens against homologous strain challenge. Vaccine,1999,17: 821-831.
162. Lu Y S, Lai W C, Pakes S P, Nie L C. A monoclonal antibody against a Pasteurella multocida outer membrane protein protects rabbits and mice against Pasteurellosis. Infect Immun,1991, 59:172-180.
163. Marandi M V, Mittal K R. Role of outer membrane protein H (ompH)- and ompA-specific monoclonal antibodies from hybridoma tumors in protection of mice against Pasteurella multocida. Infect Immun,1997,65:4502-4508
164. Magnusson H. Bacterium viscosum equi (Adsersen) in suckling pigs and its relation to Bacillus polymorphus suis (Degen) in focal interstitial nephritis in swine. Proceedings of the 11 th International Veterinary Congress:Report for Section Meetings,1931,3:488-510
165. Magyar T, King V.L, Kovacs F. Evaluation of vaccines for atrophic rhinitis—a comparison of three challenge models. Vaccine,2002,20(13-14):1797-1802
166. Manning P J, DiGiacomo R F, DeLong D. Pasteurellosis in Laboratory Animals. In: Pasteurella and Pasteurellosis. Academic Press, London,1989,263-302
167. May B J, Zhang Q, Li L L, Paustian M L, Whittam T S, Kapur V. Complete genomic sequence of Pasteurella multocida, Pm70. Proc Natl Acad Sci USA,2001,98:3460-3465
168. McDermott P F, Zhao S, Wagner D D, Simjee S, Walker R D, White D G. The food safety perspective of antibiotic resistance. Animal Biotechnology,2002,13:71-84
169. Mendes S, Carmichael K P, Nunnally J C, Glisson J R, Cheng I H, Harmon B G. Lesions resulting from attempted Shwartzman reaction in turkey poults inoculated with Pasteurella multocida lipopolysaccharide. Avian Dis,1994,38:790-796
170. Merlin C, Gardiner G, Durand S, Masters M. The Escherichia coli metD locus encodes an ABC transporter which includes Abc(MetN), YaeE (MetI), and YaeC (MetQ). J Bacteriol, 2002,184:5513-5517
171. Mizan S, Henk A, Stallings A, Maier M, Lee M D. Cloning and characterization of sialidases with 2-6' and 2-3'sialyl lactose specificity from Pasteurella multocida. J Bacteriol,2000, 182:6874-6883.
172. Mooi F R, Jansen W H, Brunings H, Gielen H, van der Heide H G, Walvoort H C, Guinee P A. Construction and analysis of Bordetella pertussis mutants defective in the production of fimbriae. Microb Pathog,1992,12:127-135
173. Morrison R B, Pijoan C, Hilley H D, Rapp V. Microorganisms associated with pneumonia in slaughter weight swine. Canadian Journal of Comparative Medicine,1985,49:129-137
174. Mullan P B, Lax A J. Pasteurella multocida toxin is a mitogen for bone cells in primary culture. Infect Immun,1996,64(5):959-965
175. Murphy A C, Rozengurt E. Pasteurella multocida toxin selectively facilitates phosphatidylinositol 4,5-bisphosphate hydrolysis by bombesin, vasopressin, and endothelin Requirement for a functional G protein. JBiol Chem,1992,267:25296-25303
176. Murray P R., Baron E J, Jorgensen J H, Pfaller M A, Yolken R H. Manual of clinical microbiology,8th edition, American Society for Microbiology, Washington, D.C.2003
177. Musser J M. Molecular population genetic analysis of emerged bacterial pathogens:selected insights. Emerg Infect Dis,1996,2(1):1-17
178. Mutters R, Ihm P, Pohl S, Frederiksen W, Mannheim W. Reclassification of the genus Pasteurella Trevisan 1887 on the basis of deoxyribonucleic acid homology, with proposals for the new species Pasteurella dagmatis, Pasteurella canis, Pasteurella stomatis, Pasteurella anatis and Pasteurella langaa. International Journal of Systematic Bacteriology,1985,35: 309-322
179. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; approved standard—2nd edition. NCCLS document M31-A. National Committee for Clinical Laboratory Standards, Wayne, Pa.2002
180. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; informational supplement. NCCLS document M31-S1. National Committee for Clinical Laboratory Standards, Wayne, Pa.2004
181.Nagai S, Spmeno S, Yagihashi T. Differention of toxigenic Pasteurella multocida from nontoxigenic isolates of Pasteurella multocida by PCR. J Clin Microbiol,1994, 32(4):1004-1010.
182. Nakai T A, Swata M. Tsuji Y. Samejima, and K. Kume. Purification of dermonecrotic toxin from a sonic extract of Pasteurella multocida SP-72 serotype D. Infect Immun,1984, 46(3):429-434
183. Ogunnariwo J A, Schryvers A B. Characterization of a novel transferrin receptor in bovine strains of Pasteurella multocida. J Bacteriol,2001,183:890-896
184. Orth JH, Blocker D, Aktories K. His 1205 and His 1223 are essential for the activity of the mitogenic Pasteurella multocida toxin. Biochemistry,2003,42(17):4971-4977
185. Pabs-Garnon L F, Soltys M A. Multiplication of Pasteurella multocida in the spleen, liver and blood of turkeys inoculated intravenously. Can J Comp Med,1971,35:147-149
186. Pandit K K and Smith J E Capsular hyaluronic acid in Pasteurella multocida type A and its counterpart in type D. Res Vet Sci,1993,54:20-24
187. Petersen S K, Foged N T. Cloning and expression of Pasteurella multocida toxin gene, toxA, in Escherichia coli. Infect Immun,1989,57,3907-3913
188. Petersen S K. The complete nucleotide sequence of the Pasteurella multocida toxin gene and evidence for a transcriptional repressor, TxaR. Mol Microbiol,1990,4(2):821-830
189. Petersen S K, Foged N T, Bording A. Recombinant derivatives of Pasteurella multocida toxin: candidates for a vaccine against progressive atrophic rhinitis. Infect Immun,1991, 59(4):1387-1393
190. Pettit R K, Ackermann M R, Rimler R B. Receptor-mediated binding of Pasteurella multocida dermonecrotic toxin to canine osteosarcoma and monkey kidney (Vero) cells. Lab Invest,1993,69(2):94-100
191. Pijoan C and Ochoa G. Interaction between a hog cholera vaccine strain and Pasteurella multocida in the production of porcine pneumonia. Journal of Comparative Pathology, 1978,88:167-170
192. Pijoan C, Morrison R B, Hilley H D. Serotyping of Pasteurella multocida isolated from swine lungs collected at slaughter. J Clin Microbiol,1983,17:1074-1076
193. Pijoan C, Lastra A, Ramirez C, Leman AD. Isolation of toxigenic strains of Pasteurella multocida from lungs of pneumonic swine. Journal of the American Veterinary Medical Association,1984,185:522-523
194. Pijoan C. Pneumonic Pasteurellosis. In Diseases of Swine,9th edn. ed. Ames:Iowa University Press.2006
195. Pizza M, Covacci A, Bartoloni A, Perugini M, Nencioni L, De Magistris MT, et al. Mutants of pertussis toxin suitable for vaccine development. Science,1989,246(4929):497-500
196. Pruimboom I M, Rimler R B, Ackermann M R, Brogden K A. Capsular hyaluronic acid-mediated adhesion of Pasteurella multocida to turkey air sac macrophages. Avian Dis, 1996,40:887-893
197. Pullinger G D, Sowdhamini R, Lax A J. Localization of functional domains of the mitogenic toxin of Pasteurella multocida. Infect Immun,2001,69(12):7839-7850
198. Pullinger G D, Bevir T, Lax A J. The Pasteurella multocida toxin is encoded within a lysogenic bacteriophage. Mol Microbiol,2004,51:255-269
199. Raemdonck D L, Tanner A C, Tolling S T, Michener S L. Antimicrobial susceptibility of Actinobacillus pleuropneumoniae, Pasteurella multocida and Salmonella choleraesuis isolates from pigs. Veterinary Record,1994,134:5-7
200. Ramdani, Adler B. Opsonic monoclonal antibodies against lipopolysaccharide (LPS) antigens of Pasteurella multocida and the role of LPS in immunity. Vet Microbiol,1991,26:335-347
201. Ram S, Cox A D, Wright J C. Neisserial lipooligosaccharide is a target for complement component c4b. Inner core phosphoethanolamine residues define C4b linkage specificity. J Biol Chem,2003,278:50853-50862
202. Rasschaert G, Houf K, Imberechts H, Grijspeerdt K, De Zutter L, Heyndrickx M. Comparison of Five Repetitive-Sequence-Based PCR Typing Methods for Molecular Discrimination of Salmonella enterica Isolates. JClin Microbiol,2005,43(8):3615-3623
203. Rebers P A, Jensen A E, Laird G A. Expression of pili and capsule by the avian strain P-1059 of Pasteurella multocida. Avian Dis,1988,32:313-318
204. Rhoades K R, Rimler R B. Effects of Pasteurella multocida endotoxins on turkey poults. Avian Dis,1987,31:523-526
205. Rhoades K R, Rimler R B. Pasteurella multocida colonization and invasion in experimentally exposed turkey poults. Avian Dis,1990,34:381-383
206. Rhoades K R, Rimler R B. Effects of Pasteurella multocida endotoxins on turkey poults. Avian Dis,1987,31:523-526
207. Richard F R. Pasteurella multocida and its role in porcine pneumonia. Animal Health Research Reviews,2007,7(1/2):13-29
208. Rimler R B, Rhoades K R. Hyaluronidase and chondroitinase activity of Pasteurella multocida serotype B:2 involved in hemorrhagic septicaemia. Vet Rec,1994,134:67-68
209. Rimler R B. Purification of a cross-protective antigen from Pasteurella multocida grown in vitro and in vivo. Avian Dis,2001,45:572-580
210. Roberts E D, Switzer W P, L' Ecuyer C. Influence of Pasteurella multocida and Mycoplasma hyorhinis (PPLO) on the histopathology of field cases of swine pneumonia. Cornell Veterinarian,1962,52:306-327
211. Rosen M N. Diseases transmitted from animals to man. Thomas Pub Illinois,1975:129-138
212. Ruffolo C G, Tennent J M, Michalski W P, Adler B. Identification, purification, and characterization of the type 4 fimbriae of Pasteurella multocida. Infect Immun,1997,65: 339-343
213. Ruffolo C G, Jost B H, Adler B. Iron-regulated outer membrane proteins of Pasteurella multocida and their role in immunity. Vet Microbiol,1998,59:123-137
214. Rutter J M. Atrophic rhinitis in swine. Adv Vet Sci Comp Med,1985,29:239-279
215. Rutter J M, Luther P D. Cell culture assay for toxigenic Pasteurella multocida from atrophic rhinitis of pigs. Vet Rec,1984,114(2):393-396
216. Salmon S A, Watts J L, Case C A, Hoffman L J, Wegener H C, Yancey Jr R J. Comparison of MICs of ceftiofur and other antimicrobial agents against bacterial pathogens of swine from the United States, Canada, and Denmark. JClin Microbiol,1995,33:2435-2444
217. Scharmann W R, Drzeniek R, Blobel H. Neuraminidase of Pasteurella multocida. Infect Immun,1970,1:319-320
218. Schenkein H A, Barbour S E, Berry C R, Kipps B, Tew J G. Invasion of human vascular endothelial cells by Actinobacillus actinomycetemcomitans via the receptor for platelet-activating factor. Infect Immun,2000,68:5416-5419
219. Schofield F W, Ingle R T. Natural and experimental hemorrhagic septicemia in swine. Annual Report of the Ontario Veterinary College for 1940,1942,29:23-27
220. Scott J P. Swine influenza. Proceedings of the ⅩⅢth International Veterinary Congress,1938, 1:479-490
221. Selander R K, Beltran P, Smith N H, Helmuth R, Rubin F A, Kopecko D J, Ferris K, Tall B D, Cravioto A, Musser J M. Evolutionary genetic relationships of clones of Salmonella serovars that cause human typhoid and other enteric fevers. Infect Immun,1990,58(7):2262-2275
222. Serino L, Virji M. Genetic and functional analysis of the phosphorylcholine moiety of commensal Neisseria lipopolysaccharide. Mol Microbiol,2002,43:437-448
223. Shivachandra S B, Kumar A A, Chaudhuri P. Molecular characterization of avian strains of Pasteurella multocida serogroup-A:1 based on amplification of repetitive regions by PCR. Comp Immunol Microbiol Infect Dis.2008,31(1):47-62
224. Snipes K P, Hirsh D C. Association of complement sensitivity with virulence of Pasteurella multocida isolated from turkeys. Avian Dis,1986,30:500-504
225. Snipes K P, Ghazikhanian G Y, Hirsh D C. Fate of Pasteurella multocida in the blood vascular system of turkeys following intravenous inoculation:comparison of an encapsulated, virulent strain with its a virulent, a capsular variant. Avian Dis,1987,31:254-259.
226. Snipes K P, Hansen L M, Hirsh D C. lasma-and iron regulated expression of high molecular weight outer membrane proteins by Pasteurella multocida. Am J Vet Res,1988, P 49:1336-1338
227. Spray R S. The bacteria in normal and diseased lungs of swine. J Infect Dis.1922,31:10-21
228. Steenbergen S M, Lichtensteiger C A, Caughlan R, Garfinkle J, Fuller T E, Vimr E R. Sialic acid metabolism and systemic pasteurellosis. Infect Immun,2005,73:1284-1294
229. Staddon J M, Chanter N, Lax A J, Higgins T E, Rozengurt E. Pasteurella multicoda toxin, a potent mitogen, stimulates protein kinase C-dependent and -independent protein phosphorylation in Swiss 3T3 cells. JBiol Chem,1990,265(34):11841-11848
230. St Michael F, Li J, Cox A D. Structural analysis of the core oligosaccharide from Pasteurella multocida strain X73. Carbohydr Res,2005,340:1253-1257
231. Straus D C, Purdy C W. In vivo production of neuraminidase by Pasteurella haemolytica A1 in goats after transthoracic challenge. Infect Immun,1994,62:4675-4678
232. Straw B E, Dewey C E, Erickson E D. Interpreting culture reports from swine lungs. Swine Health and Production,1996,4:200-201
233. Tabatabai LB, Zehr E S. Identification of five outer membrane-associated proteins among cross-protective factor proteins of Pasteurella multocida. Infect Immun,2004,72:1195-1198
234. Tatum F M, Yersin A G, Briggs R E. Construction and virulence of a Pasteurella multocida fhaB2 mutant in turkeys. Microb Pathog,2005,39:9-17
235. To H, Someno S, Nagai S. Development of a genetically modified nontoxigenic Pasteurella multocida toxin as a candidate for use in vaccines against progressive atrophic rhinitis in pigs. Am J Vet Res,2005,66:113-118
236. Townsend K M, O'Boyle D, Phan T T, Hanh T X, Wijewardana T G, Wilkie I, Trung N T, Frost A J. Acute septicaemic pasteurellosis in Vietnamese pigs. Vet Microbiol,1998,63: 205-215
237. Townsend K M, Boyce J D, Chung J Y, Frost A J, Adler B. Genetic organization of Pasteurella multocida cap loci and development of a multiplex capsular PCR typing system. J Clin Microbiol,2001,39:924-929
238. Toyotsugu Nakai, Akira Sawata, Masayoshi, et al. Characterization of dermonecrotic toxin produced by serotype D strains of Pasteurella multocida. Am J Vet Res,1984,45(11): 2410-2413
239. Truscott W M, Hirsh D C. Demonstration of an outer membrane protein with antiphagocytic activity from Pasteurella multocida of avian origin. Infect Immun,1988,56:1538-1544
240. Tsuji M, Matsumoto M. Pathogenesis of fowl cholera:influence of encapsulation on the fate of Pasteurella multocida after intravenous inoculation into turkeys. Avian Dis,1989, 33:238-247.
241.Vasfi Marandi M, Mittal K R. Role of outer membrane protein H (OmpH)-and OmpA-specific monoclonal antibodies from hybridoma tumors in protection of mice against Pasteurella multocida. Infect Immun,1997,65:4502-4508
242. Vecht U, Wisselink H J, van Dijk J E, Smith H E. Virulence of Streptococcus suis type 2 strains in newborn germfree pigs depends on phenotype. Infect Immun,1992,60:550-556
243. Veken J W, Oudega B, Luirink J, De Graaf F K. Binding of bovine transferrin by Pasteurella multocida serotype B:2,5, a strain which causes haemorrhagic septicaemia in buffalo and cattle. Microb Lett,1994,115:253-258
244. Vera Lizarazo Y A, Rodn'guez Ferri E F, Martin de la Fuente A J, Gutie'rrez Martin C B. Evaluation of changes in antimicrobial susceptibility patterns of Pasteurella multocida subsp multocida isolates from pigs in Spain in 1987-1988 and 2003-2004. American Journal of Veterinary Research,2006,67:663-668
245. Verma N D. Pasteurella multocida B:2 in haemorrhagic septicemia outbreak in pigs in India. Veterinary Record,1988,123:63
246. Walsh C, Fanning S. Antimicrobial resistance in foodborne pathogens--a cause for concern? Curr Drug Targets,2008,9:808-815
247. Ward P N, Miles A J, Sumner I G., Thomas L H, Lax A J. Activity of the Mitogenic Pasteurella multocida Toxin Requires an Essential C-Terminal Residue Infect Immun, 1998,66(12):5636-5642
248. White D G, Zhao S, Simjee S, Wagner D D, McDermott P F. Antimicrobial resistance of foodborne pathogens. Microbes Infect,2002,4:405-412
249. White D J, Jolley W L, Purdy C W, Straus D C. Extracellular neuraminidase production by a Pasteurella multocida A-3 strain associated with bovine pneumonia. Infect Immun,1995, 63:1703-1709
250. Wilson B A, Zhu X, Ho M, Lu L. Pasteurella multocida toxin activates the inositol triphosphate signaling pathway in Xenopus oocytes via G(q)alpha-coupled phospholipase C-betal. JBiol Chem, (1997)272:1268-1275
251. Wijewardana T G, Sutherland A D. Bactericidal activity in the sera of mice vaccinated with Pasteurella multocida type A. Vet Microbiol,1990,24:55-62
252. Williams K J, Halkes K M, Kamerling J P, DeAngelis P L. Critical elements of oligosaccharide acceptor substrates for the Pasteurella multocida hyaluronan synthase. JBiol Chem,2006,281:5391-5397
253. Wozniak D J, Hsu L Y, Galloway D R. His-426 of the Pseudomonas aeruginosa exotoxin A is required for ADP-ribosylation of elongation factor II. Proc Natl Acad Sci USA,1988,85(23): 8880-8884
254. Yamamoto J, Sakano T, Shimizu M. Drug resistance and R plasmids in Pasteurella multocida isolates from swine. Microbiology and Immunology,1990,34:715-721
255. Yoshimura H, Ishimaru M, Endoh Y S, Kojima A. Antimicrobial susceptibility of Pasteurella multocida isolated from cattle and pigs. J Vet Med B,2001,48:555-560
256. Yu H, Chokhawala H, Karpel R, Wu B, Zhang J, Zhang Y, Jia Q, Chen X. A multifunctional Pasteurella multocida sialyltransferase:a powerful tool for the synthesis of sialoside libraries. J Am Chem Soc,2005,127:17618-17619