山东省猪源致病性性沙门氏菌的分离鉴定与耐药性分析
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摘要
近年来,随着养猪业的发展,猪病的种类和数量有上升趋势,给养殖业造成巨大的经济损失,沙门氏菌病尤为突出。沙门氏菌极易产生耐药性,近年来临床上的不规范用药进一步加剧了耐药性的发展,沙门氏菌耐药菌株越来越多,耐药谱越来越广,有的菌株甚至对尚未广泛用于兽医临床的新型抗生素也表现出很强的耐药性。另外,动物源性携带耐药质粒的肠道菌可通过畜产品的加工、感染等过程传播给人类,因而耐药性沙门氏菌不但给兽医临床治疗带来了困难,加剧了治疗和用药的恶性循环,而且对人类健康构成了潜在威胁。对此,本研究对山东省不同地区猪源性沙门氏菌病的流行情况和致病性沙门氏菌的耐药性状况进行了较系统的研究。对猪源性沙门氏菌进行分离鉴定、致病性试验,同时对沙门氏菌入侵基因invH及氨基糖甙类药物耐药基因aph(3′)-IIa进行了检测,以期探明山东省不同地区猪源性沙门氏菌病的流行情况和耐药现状,从而为有效控制沙门氏菌病的发生提供可靠的理论依据。本研究共分为三个试验:
试验一山东省猪源性沙门氏菌的分离鉴定及入侵基因invH的检测
从山东省具有代表性的七个不同地区的大型猪场的201份检样中分离到135株疑似沙门氏菌,然后通过常规生化鉴定及ATB微生物鉴定系统鉴定,最终确定95株为沙门氏菌;对95株沙门氏菌进行沙门氏菌入侵基因invH的PCR扩增,结果87株分离菌扩出特异性条带,扩增效率为91.6%(87/95)。
从85株invH基因阳性的沙门氏菌中随机选取25株进行致病性试验,结果发现,25株中有23株有致病性(占92.0%);其中有13株(WJS仔3-2、WWS哺3-1、JZS42<仔>、JZS18<公>、JZS7<保>、JYS133<肥>、LJS5<后>、WJS后1-1、WJS哺2-3、LJS16<保>、PLS24-3<公>、PLS7-1<土>、PLS27-1<后>)对小白鼠的致死率均高于80%,与invH基因的入侵特性相符。
试验二山东省猪源性沙门氏菌多重耐药性研究
采用kirby-Bauer琼脂扩散法,对95株沙门氏菌分离株分别选用28种药物进行敏感性试验,结果表明,山东省不同地区猪场中存在的沙门氏菌对27种药物均有不同程度的耐受,其中对苯唑西林、乳酸TMP、舒巴坦、利福平、氟苯尼考、克林霉素、青霉素G、土霉素的耐药性较高,耐10种以上药物的菌株占69.5%;多重耐药率最高的地区为鲁北地区,鲁西南地区,说明这两个地区药物存在滥用现象,这与调查的结果想吻合。
试验三猪沙门氏菌氨基糖甙类抗生素耐药基因aph(3′)-IIa的检测
选取经生化鉴定、invH基因鉴定阳性,且经药敏试验对氨基糖甙类抗生素耐药的19株沙门氏菌进行了氨基糖甙类抗生素耐药基因aph(3′)-IIa的检测,结果有14株被检为阳性(14/19),阳性符合率为73.7%,同时对耐药基因aph(3′)-IIa的序列进行了分析,结果与Genbank上发表的AF078924.1、AF188331.1、AY333434.1、AY598820.1、DQ842000.1的耐药基因aph(3′)-IIa的序列比较后发现,同源率为100%。
Recent years, the infection diseases of swine was becoming more and more serious. However, some diseases caused by bacteria, especial Salmonella, are more prevalent and have caused numerous losses in swine industry. Most strains of Salmonella are more and more widespread. The spectrum of the resistence becomes wider and wider. Some strains even could resist the new antibiotics which have not been used in animal. Bacteria with drug-resistant plasmid could be transferred from animal to human, so the abuse of large dosage of antibiotics not only makes it difficult to cure the disease, but also makes it latent harm to humankind. In this paper, we report the isolation, purification, identification, invH gene amplification and pathogenicity of Salmonella in swine. The interrelation between drug-resistance and aminoglycosides-resistance gene was investigated. In order to show the inspection and drug-resistance of Samolella in Shandong province and provide the therotical basis for controlling Salmonlella. The study includes three parts:
PartⅠ: Separation and identification of pathogenica swine Salmonella and invasion gene of invH
201 samples were collected from seven large hogpen in different parts of Shandong province and gained 135 bacteria. All were identified by culture, staining, biochemical test and ATB biochemical-system. 95 strains were identified Salmolella in the end; The invH gene of 95 strains were amplified. The result was that 87 strains were identified. The positive compatible rate was 91.6%(87/95).
In the end, Choosing 25 Salmonella which were identified by biochemical test and invH gene PCR to test the pathogen of separated Salmonella. The result was that the strains which include WJS3-2, WWS3-1, JZS42, JZS18、JZS7, JYS133, LJS5, WJS1-1, WJS2-3、LJS16、PLS24-3、PLS7-1、PLS27-1 were pathogenic to white mouse. The death rate was over 80%. At the same time, There were Only two strains of no-pathogen to the white mouse. The payhogenic rate was 92.0% (23/25). The result was matched with the invasion characteristic of invH gene.
Part II: Inspection of Antibiotic Resistance of pathogenic Salmonella from Swine
With 27 kinds of drug sensitivity slips of clinical frequently used antibiotic by kirby-Bauer mean to test the drug sensitivity for the isolated 95 strains, we found that the sensitivity drug of the Salmonella isolated from different hogpen was resembled to the drug, and the sensitivity drug of the Salmoella isolated from the same hoghen was the same, too. At the same time, the separated strains of different parts were some difference. Results showed that isolated strains resist 28 types of drugs. The high drug-resistance of all strains was Proctaphlin, Trimethoprin, Sulbactam, Rifampicin, Florfenicol, Clindamycin, Penicilin G, Terramycin. The multi-resistance was over ten-resistance. The percentage of the resistance was 69.5% in the 95 strains. The hightest distances of drug-resistance rate were the north 2 and west-south 2 of Shandong province. The condition were matched with the drugs were abused in the two parts.
Part III: Study on the molecular epidemiology of aph(3′)-IIa gene of pathogenic Salmonella
19 strains were choosen from the isolated sample, at the same time, the19 strains were positive by biochemical test, the identificatione by invH gene test and Aminoglycosides-resistance test. The 19 strains were used to test aph(3′)-IIa gene. The result was that 14 positive strains were identificated from the tested strains. Compared to the results of the drug-susceptibility tests, the method of PCR showed 73.7% concordance on positive rate. Detected aph(3′)-IIa gene of 3 strain which were from the 13 positive strains had the same gene sequences as the genes (AF078924.1、AF188331.1、AY333434.1、AY598820.1、DQ842000.1) published in GenBank. The result was that the isogeny rate was 100%.
试验一山东省猪源性沙门氏菌的分离鉴定及入侵基因invH的检测
从山东省具有代表性的七个不同地区的大型猪场的201份检样中分离到135株疑似沙门氏菌,然后通过常规生化鉴定及ATB微生物鉴定系统鉴定,最终确定95株为沙门氏菌;对95株沙门氏菌进行沙门氏菌入侵基因invH的PCR扩增,结果87株分离菌扩出特异性条带,扩增效率为91.6%(87/95)。
从85株invH基因阳性的沙门氏菌中随机选取25株进行致病性试验,结果发现,25株中有23株有致病性(占92.0%);其中有13株(WJS仔3-2、WWS哺3-1、JZS42<仔>、JZS18<公>、JZS7<保>、JYS133<肥>、LJS5<后>、WJS后1-1、WJS哺2-3、LJS16<保>、PLS24-3<公>、PLS7-1<土>、PLS27-1<后>)对小白鼠的致死率均高于80%,与invH基因的入侵特性相符。
试验二山东省猪源性沙门氏菌多重耐药性研究
采用kirby-Bauer琼脂扩散法,对95株沙门氏菌分离株分别选用28种药物进行敏感性试验,结果表明,山东省不同地区猪场中存在的沙门氏菌对27种药物均有不同程度的耐受,其中对苯唑西林、乳酸TMP、舒巴坦、利福平、氟苯尼考、克林霉素、青霉素G、土霉素的耐药性较高,耐10种以上药物的菌株占69.5%;多重耐药率最高的地区为鲁北地区,鲁西南地区,说明这两个地区药物存在滥用现象,这与调查的结果想吻合。
试验三猪沙门氏菌氨基糖甙类抗生素耐药基因aph(3′)-IIa的检测
选取经生化鉴定、invH基因鉴定阳性,且经药敏试验对氨基糖甙类抗生素耐药的19株沙门氏菌进行了氨基糖甙类抗生素耐药基因aph(3′)-IIa的检测,结果有14株被检为阳性(14/19),阳性符合率为73.7%,同时对耐药基因aph(3′)-IIa的序列进行了分析,结果与Genbank上发表的AF078924.1、AF188331.1、AY333434.1、AY598820.1、DQ842000.1的耐药基因aph(3′)-IIa的序列比较后发现,同源率为100%。
Recent years, the infection diseases of swine was becoming more and more serious. However, some diseases caused by bacteria, especial Salmonella, are more prevalent and have caused numerous losses in swine industry. Most strains of Salmonella are more and more widespread. The spectrum of the resistence becomes wider and wider. Some strains even could resist the new antibiotics which have not been used in animal. Bacteria with drug-resistant plasmid could be transferred from animal to human, so the abuse of large dosage of antibiotics not only makes it difficult to cure the disease, but also makes it latent harm to humankind. In this paper, we report the isolation, purification, identification, invH gene amplification and pathogenicity of Salmonella in swine. The interrelation between drug-resistance and aminoglycosides-resistance gene was investigated. In order to show the inspection and drug-resistance of Samolella in Shandong province and provide the therotical basis for controlling Salmonlella. The study includes three parts:
PartⅠ: Separation and identification of pathogenica swine Salmonella and invasion gene of invH
201 samples were collected from seven large hogpen in different parts of Shandong province and gained 135 bacteria. All were identified by culture, staining, biochemical test and ATB biochemical-system. 95 strains were identified Salmolella in the end; The invH gene of 95 strains were amplified. The result was that 87 strains were identified. The positive compatible rate was 91.6%(87/95).
In the end, Choosing 25 Salmonella which were identified by biochemical test and invH gene PCR to test the pathogen of separated Salmonella. The result was that the strains which include WJS3-2, WWS3-1, JZS42, JZS18、JZS7, JYS133, LJS5, WJS1-1, WJS2-3、LJS16、PLS24-3、PLS7-1、PLS27-1 were pathogenic to white mouse. The death rate was over 80%. At the same time, There were Only two strains of no-pathogen to the white mouse. The payhogenic rate was 92.0% (23/25). The result was matched with the invasion characteristic of invH gene.
Part II: Inspection of Antibiotic Resistance of pathogenic Salmonella from Swine
With 27 kinds of drug sensitivity slips of clinical frequently used antibiotic by kirby-Bauer mean to test the drug sensitivity for the isolated 95 strains, we found that the sensitivity drug of the Salmonella isolated from different hogpen was resembled to the drug, and the sensitivity drug of the Salmoella isolated from the same hoghen was the same, too. At the same time, the separated strains of different parts were some difference. Results showed that isolated strains resist 28 types of drugs. The high drug-resistance of all strains was Proctaphlin, Trimethoprin, Sulbactam, Rifampicin, Florfenicol, Clindamycin, Penicilin G, Terramycin. The multi-resistance was over ten-resistance. The percentage of the resistance was 69.5% in the 95 strains. The hightest distances of drug-resistance rate were the north 2 and west-south 2 of Shandong province. The condition were matched with the drugs were abused in the two parts.
Part III: Study on the molecular epidemiology of aph(3′)-IIa gene of pathogenic Salmonella
19 strains were choosen from the isolated sample, at the same time, the19 strains were positive by biochemical test, the identificatione by invH gene test and Aminoglycosides-resistance test. The 19 strains were used to test aph(3′)-IIa gene. The result was that 14 positive strains were identificated from the tested strains. Compared to the results of the drug-susceptibility tests, the method of PCR showed 73.7% concordance on positive rate. Detected aph(3′)-IIa gene of 3 strain which were from the 13 positive strains had the same gene sequences as the genes (AF078924.1、AF188331.1、AY333434.1、AY598820.1、DQ842000.1) published in GenBank. The result was that the isogeny rate was 100%.
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