女性淋球菌无症状感染的相关因素研究
|
摘要
第一部分淋球菌的基因分型、毒力岛分类及与女性无症状感染关系的研究
目的评价Opa分型及NG-MAST对淋球菌分离株进行基因分型的能力及性伴侣分离淋球菌基因型别之间的关系，研究淋球菌不同基因型别的毒力岛类型及其所引起女性无症状感染关系。
方法12对性接触者淋球菌分离株培养鉴定后Opa基因以HpaⅡ酶切及聚丙烯酰胺凝胶电泳银染显色分析；12株男性标本和81株女性标本PCR扩增por和tbpB后测序用NG-MAST方法从分子水平上进行基因分型，并用ClustalX软件做进化树分析；并对毒力岛分类与女性无症状感染关系进行了研究。
结果12对性接触患者分离株中，NG-MAST区分出10种ST型，而使用Opa分型则呈现12种OT型；新发现的ST(217-679)是国内特有的流行株。武汉地区女性感染的81株野生株中，GGI阳性菌株占了64株(80．43％)；无症状组有GGI阳性株也有GGI阴性株，有症状组也是如此。
结论患者-性伴组除了45／46之外每对菌株的ST型及OT型均相同，表明患者与性伴相互接触传染。Opa-typing及NG-MAST可区分性关系网中的淋球菌菌株，二种方法分型结果总的趋向一致。Opa分型能力高于NG-MAST，ST型别可进一步的分成opa-types(OT)亚型。GGI毒力岛与女性症状感染之间并无明显的相关性，即女性有脓性分泌物感染并不是感染了强毒力的菌株所致。
第二部分衣原体感染、性激素水平等因素与女性无症状感染关系的研究
目的探讨女性淋球菌感染症状与衣原体感染及体内性激素水平等因素之间的关系。
方法选择136例无明显症状女性淋病患者为观察组，45例有症状者为对照组，检测宫颈分泌物衣原体及淋球菌DNA；放射免疫法测定E2和P浓度；用RT-PCR和ELISA的方法在mRNA水平和蛋白水平检测炎症因子TNF-α、IL-1β的表达。用SPSS12．0软件进行统计学分析。
结果淋病的无明显症状感染与衣原体感染无显著相关性，但其炎症因子TNF-α、IL-1β减少与血清孕激素水平升高的相关性具有统计学意义。
结论女性淋病患者体内孕激素水平的增高可能是导致无症状感染的重要原因。
第三部分孕激素体外调节Ngo-PMNs炎症反应的作用机制研究
目的选择了有症状组和无症状组的非独特NG-MAST亚型各3种菌株，进一步研究孕激素在这些淋球菌野生株引起的中性粒细胞炎症反应的调节作用，探讨其作用差异及信号转导的可能机制。
方法分离人外周血中性粒细胞(PMNs)，用免疫荧光和RT-PCR检测PMNs上PR的表达：细胞维持在含10％热灭活胎牛血清的RPMI培养液中，细胞浓度为5×10~6，淋球菌培养过夜后重悬在PBS中调整为OD_(600)=0．15(～10~8 gonococci ml~(-1))，感染复数(MOI)为10 bacteria／cell，在孕激素作用的不同时段用荧光定量PCR的方法检测iNOS，eNOS，TNF-a和IL-1β的变化，用Western Blot测定iNOS，eNOS，Akt和p-Akt(Ser473)蛋白水平，比较分析其差异。
结果我们通过RT-PCR和免疫荧光的方法发现人的外周中性粒细胞并不表达经典的PR受体；孕激素能抑制iNOS，TNF-α和IL-1β的mRNA表达，在有症状组NgoST2951、ST735、ST436和无症状组ST809、ST369、ST2948中并没有显著差别；孕激素显著下调了iNOS蛋白的表达水平，然而eNOS蛋白没有检测到显著的改变；在孕激素处理前后没有能观察到磷酸化的Akt蛋白，总的Akt也没有改变。
结论孕激素的压力导致PMNs中加剧iNOS表达的抑制和PMNs前炎症因子的下调，而这种作用是不依赖于PR介导受体途径和Akt信号通路。
第四部分孕激素体外调节Ngo-PMNs呼吸爆发、凋亡应答的机制研究
目的研究孕激素体外调节淋球菌引起的中性粒细胞呼吸爆发和凋亡的作用。
方法分离人外周血中性粒细胞，分别用孕激素和十字孢碱处理，十字孢碱作为阳性对照。在0，3，8，12小时等时段用荧光定量RT-PCR分别测定各组中性粒细胞中凋亡抑制蛋白cIAP2和XIAP的表达水平；同时用流式细胞仪检测PMNs凋亡，用鲁米诺化学发光法检测淋球菌ST2951株刺激PMNs后呼吸爆发。
结果cIAP2在孕激素处理3h后显著上调而XIAP和ST2951+medium组相比上调轻微；cIAP2在十字孢碱组是下调的。此外，我们发现孕激素对淋球菌ST2951刺激后的中性粒细胞有明显的延迟凋亡作用，尤其是在12h的时候；10ng／mL的孕激素对中性粒细胞的呼吸爆发并没有显著的影响，而十字孢碱加强了淋球菌刺激后中性粒细胞超氧负离子的产生。
结论孕激素对淋球菌引起的中性粒细胞炎症反应有很重要的调节作用，孕激素介导的延迟感染了淋球菌的中性粒细胞凋亡可能是其逃避天然免疫和建立女性生殖道长期的低水平感染的重要机制，可能在女性无症状感染中起重要作用。
PartⅠStudy on Classification of the gonococcal genetic island ofdifferent genotypes and the relationship of GGI with femalegonococcal asymptomatic infections
Objective Two molecular epidemiology methods which was Opa Genotyping andNG-MAST Genotyping were carried out to identify the genomic species of Neisseriagonorrhoeae.To evaluate effectivity of two molecular epidemiology methods and study therelationship between sex partner and different genotypes and female gonococcalasymptomatic infections.
Methods The methods of Opa Genotyping and NG-MAST Genotyping was used todifferentiate 12 strains from male and 81 strains from female patients who attended theoutpatients of sexually transmitted disease clinics and the relationship between differentgenotypes and phenotypes was studied. Furthermore, the genetic diversity and phylogeneticrelationship of the 12 paired strains was investigated using the Clustaix software, whichwas based on the gene sequences information.
Results 12 paired strains of Neisseria gonorrhoeae were classified into 10 ST genotypes byusing NG-MAST genotyping,whereas the specimens were classified into 12 OT Opagenotyping genotypes by using Opa genotyping; a new-found ST genotype (217-679)was aspecific epidemic strain in domestic. Some 80.43% of the 81 strains contained the island,different isolates from female asymptomatic infections carried different gonococcal geneticislands(positive and negative),so were the isolates from symptomatic infections.Conclusion Genotypes of each strains from patient-sex partner besides 45/46 are the samewhich indicated that contagious infection exist between patient and sex partner.Strainswithin sexual networks could be differentiated by Opa genotyping and NG-MASTgenotyping analysis. General agreement was found between these two techniques.Opa genotyping was more effective than NG-MAST genotyping in identify the genomic speciesof Neisseria gonorrhoeae.ST genotype could be further classfied into different opa-types.Different isolates carried different gonococcal genetic islands(Pathogenicity island) andcertain phenotypes, and there were little relationship between GGI and symptomaticgonococcal infections.
PartⅡStudy of the relationship between the symptom of femalegonococcal infections, Chlamydia trachomatis infections and sexhormone
Objective To study the relationship between the symptom of female gonococcalinfections, Chlamydia trachomatis infections and sex hormone.
Methods We studied 136 gonorrhea patients with less symptomatic (asymptomatic group)and 45 with symptomatic(symptomatic group ). Their endocervical specimens were testedfor Chlamydia trachomatis, Neisseria gonorrhoeae by PCR, the levels of TNF-αandIL-1βby ELISA. Serum progesterone (P) and estradiol(E2) levels were measured by radioimmunoassay (RIA). The results were evaluated by SPSS for Windows (version 12.0) usingstatistical analysis.
Results Chlamydia trachomatis have no relationgnship with female asymptomaticgonococcal infections. However, the relationship between the decreased levels of TNF-α、IL-1βand the increased levels of progesterone was considered statistical significant at P＜0.05.
Conclusion Progesterone may play a key role in female less symptomatic gonococcalinfections by down-regulatd inflammatory response.
PartⅢEffect and mechanism of progesterone on PMNinflammatory responses to wild-type gonococci in vitro
Objective We used 3 types of strains associated with female symptomatic Infections and 3with asymptomatic Infections to investigate the modulation effects of progesterone on PMNinflammatory responses to gonoccocus.
Methods PMNs were isolated from Heparinized peripheral blood from healthy volunteers.After incubation of PMNs With 50 ng/mL 17β-estradiol for 6 hours at 37℃with 5% CO2,PR mRNA expression was determined by RT-PCR and immunofluorescence. Additionallythe effect of progesterone on N. gonorrhoeae-challenged polymorphonuclear leukocytesinflammatory responses at various time points were assayed by real-time RT-PCR. Akt,p-Akt (Ser473), iNOS and eNOS were detected respectively by Western blot.
Results Among these non-unique multiple isolates from asymptomatic women(ST2951,ST735 and ST436) and from symptomatic women(ST809,ST369 and ST2948) we found nosignificant difference in Ngo-PMNs inflammatory responses. In vitro PMNs infectionexperiments, progesterone suppressed expression of iNOS、TNF-α、IL-1βtranscript andiNOS protein significantly(P＜0.01) while eNOS expression revealed a slight change. Wefound that human peripheral blood PMNs did not express the classical progesteronereceptor and the role of progesterone was independent of Akt signaling pathway.Conclusions Gonococci are susceptible to progesterone or their downstream effects invitro. Progesterone induced down-regulated expression of pro-inflammatory cytokines suchas iNOS etc., which is independent of akt signaling pathway in Ngo challanged PMNs.
PartⅣEffect of progesterone on gonococci-induced apoptosisand respiratory burst of human polymorphonuclear leucocytesin vitro
Objective To investigate the regulatory effect of progesterone on apoptosis and oxidativeburst activity of polymorphonuclear leucocytes(PMNs) challenged by Neisseriagonorrhoeae (Ngo) in vitro.
Methods Isolated PMNs were incubated with progesterone or staurosporine. Staurosporinewas used as a positive control for our vitro model. Expression levels of inhibitory apoptosisproteins (IAPs), cellular IAP2(cIAP2) and X-linked IAP (XIAP) were determined byreal-time PCR. Additionally, PMNs apoptosis at various time points (3, 8, 12 and 24h) wereassayed by flow cytometry. Luminol amplified chemiluminescence methods were used toquantify the oxidative burst function of PMNs challenged with Ngo ST2951.
Results cIAP2 was up-regulated significantly in PMNs with progesterone treatment in 3hand XIAP was up-regulated slightly compared to the medium+ST2951 group, while cIAP2was down-regulated in staurosporine-challenged PMNs. Additionally we foundprogesterone delayed the onset of apoptosis activity in Ngo ST2951 challenged PMNs,notably at 12h. No statistically significant changes in PMNs oxidative burst activity wereobserved at 10 ng/mL level of progesterone. Staurosporine enhanced the production ofsuperoxide anion (respiratory burst) of human PMNs stimulated by Ngo.
Conclusion Progesterone plays an important regulatory role in the interaction of PMNs andNgo. Delayed PMNs apoptosis induced by progesterone presumably acts as a mechanismfor Ngo to avoid the innate immune response and establish long-term, low-level infection inthe female reproductive tract.
目的评价Opa分型及NG-MAST对淋球菌分离株进行基因分型的能力及性伴侣分离淋球菌基因型别之间的关系，研究淋球菌不同基因型别的毒力岛类型及其所引起女性无症状感染关系。
方法12对性接触者淋球菌分离株培养鉴定后Opa基因以HpaⅡ酶切及聚丙烯酰胺凝胶电泳银染显色分析；12株男性标本和81株女性标本PCR扩增por和tbpB后测序用NG-MAST方法从分子水平上进行基因分型，并用ClustalX软件做进化树分析；并对毒力岛分类与女性无症状感染关系进行了研究。
结果12对性接触患者分离株中，NG-MAST区分出10种ST型，而使用Opa分型则呈现12种OT型；新发现的ST(217-679)是国内特有的流行株。武汉地区女性感染的81株野生株中，GGI阳性菌株占了64株(80．43％)；无症状组有GGI阳性株也有GGI阴性株，有症状组也是如此。
结论患者-性伴组除了45／46之外每对菌株的ST型及OT型均相同，表明患者与性伴相互接触传染。Opa-typing及NG-MAST可区分性关系网中的淋球菌菌株，二种方法分型结果总的趋向一致。Opa分型能力高于NG-MAST，ST型别可进一步的分成opa-types(OT)亚型。GGI毒力岛与女性症状感染之间并无明显的相关性，即女性有脓性分泌物感染并不是感染了强毒力的菌株所致。
第二部分衣原体感染、性激素水平等因素与女性无症状感染关系的研究
目的探讨女性淋球菌感染症状与衣原体感染及体内性激素水平等因素之间的关系。
方法选择136例无明显症状女性淋病患者为观察组，45例有症状者为对照组，检测宫颈分泌物衣原体及淋球菌DNA；放射免疫法测定E2和P浓度；用RT-PCR和ELISA的方法在mRNA水平和蛋白水平检测炎症因子TNF-α、IL-1β的表达。用SPSS12．0软件进行统计学分析。
结果淋病的无明显症状感染与衣原体感染无显著相关性，但其炎症因子TNF-α、IL-1β减少与血清孕激素水平升高的相关性具有统计学意义。
结论女性淋病患者体内孕激素水平的增高可能是导致无症状感染的重要原因。
第三部分孕激素体外调节Ngo-PMNs炎症反应的作用机制研究
目的选择了有症状组和无症状组的非独特NG-MAST亚型各3种菌株，进一步研究孕激素在这些淋球菌野生株引起的中性粒细胞炎症反应的调节作用，探讨其作用差异及信号转导的可能机制。
方法分离人外周血中性粒细胞(PMNs)，用免疫荧光和RT-PCR检测PMNs上PR的表达：细胞维持在含10％热灭活胎牛血清的RPMI培养液中，细胞浓度为5×10~6，淋球菌培养过夜后重悬在PBS中调整为OD_(600)=0．15(～10~8 gonococci ml~(-1))，感染复数(MOI)为10 bacteria／cell，在孕激素作用的不同时段用荧光定量PCR的方法检测iNOS，eNOS，TNF-a和IL-1β的变化，用Western Blot测定iNOS，eNOS，Akt和p-Akt(Ser473)蛋白水平，比较分析其差异。
结果我们通过RT-PCR和免疫荧光的方法发现人的外周中性粒细胞并不表达经典的PR受体；孕激素能抑制iNOS，TNF-α和IL-1β的mRNA表达，在有症状组NgoST2951、ST735、ST436和无症状组ST809、ST369、ST2948中并没有显著差别；孕激素显著下调了iNOS蛋白的表达水平，然而eNOS蛋白没有检测到显著的改变；在孕激素处理前后没有能观察到磷酸化的Akt蛋白，总的Akt也没有改变。
结论孕激素的压力导致PMNs中加剧iNOS表达的抑制和PMNs前炎症因子的下调，而这种作用是不依赖于PR介导受体途径和Akt信号通路。
第四部分孕激素体外调节Ngo-PMNs呼吸爆发、凋亡应答的机制研究
目的研究孕激素体外调节淋球菌引起的中性粒细胞呼吸爆发和凋亡的作用。
方法分离人外周血中性粒细胞，分别用孕激素和十字孢碱处理，十字孢碱作为阳性对照。在0，3，8，12小时等时段用荧光定量RT-PCR分别测定各组中性粒细胞中凋亡抑制蛋白cIAP2和XIAP的表达水平；同时用流式细胞仪检测PMNs凋亡，用鲁米诺化学发光法检测淋球菌ST2951株刺激PMNs后呼吸爆发。
结果cIAP2在孕激素处理3h后显著上调而XIAP和ST2951+medium组相比上调轻微；cIAP2在十字孢碱组是下调的。此外，我们发现孕激素对淋球菌ST2951刺激后的中性粒细胞有明显的延迟凋亡作用，尤其是在12h的时候；10ng／mL的孕激素对中性粒细胞的呼吸爆发并没有显著的影响，而十字孢碱加强了淋球菌刺激后中性粒细胞超氧负离子的产生。
结论孕激素对淋球菌引起的中性粒细胞炎症反应有很重要的调节作用，孕激素介导的延迟感染了淋球菌的中性粒细胞凋亡可能是其逃避天然免疫和建立女性生殖道长期的低水平感染的重要机制，可能在女性无症状感染中起重要作用。
PartⅠStudy on Classification of the gonococcal genetic island ofdifferent genotypes and the relationship of GGI with femalegonococcal asymptomatic infections
Objective Two molecular epidemiology methods which was Opa Genotyping andNG-MAST Genotyping were carried out to identify the genomic species of Neisseriagonorrhoeae.To evaluate effectivity of two molecular epidemiology methods and study therelationship between sex partner and different genotypes and female gonococcalasymptomatic infections.
Methods The methods of Opa Genotyping and NG-MAST Genotyping was used todifferentiate 12 strains from male and 81 strains from female patients who attended theoutpatients of sexually transmitted disease clinics and the relationship between differentgenotypes and phenotypes was studied. Furthermore, the genetic diversity and phylogeneticrelationship of the 12 paired strains was investigated using the Clustaix software, whichwas based on the gene sequences information.
Results 12 paired strains of Neisseria gonorrhoeae were classified into 10 ST genotypes byusing NG-MAST genotyping,whereas the specimens were classified into 12 OT Opagenotyping genotypes by using Opa genotyping; a new-found ST genotype (217-679)was aspecific epidemic strain in domestic. Some 80.43% of the 81 strains contained the island,different isolates from female asymptomatic infections carried different gonococcal geneticislands(positive and negative),so were the isolates from symptomatic infections.Conclusion Genotypes of each strains from patient-sex partner besides 45/46 are the samewhich indicated that contagious infection exist between patient and sex partner.Strainswithin sexual networks could be differentiated by Opa genotyping and NG-MASTgenotyping analysis. General agreement was found between these two techniques.Opa genotyping was more effective than NG-MAST genotyping in identify the genomic speciesof Neisseria gonorrhoeae.ST genotype could be further classfied into different opa-types.Different isolates carried different gonococcal genetic islands(Pathogenicity island) andcertain phenotypes, and there were little relationship between GGI and symptomaticgonococcal infections.
PartⅡStudy of the relationship between the symptom of femalegonococcal infections, Chlamydia trachomatis infections and sexhormone
Objective To study the relationship between the symptom of female gonococcalinfections, Chlamydia trachomatis infections and sex hormone.
Methods We studied 136 gonorrhea patients with less symptomatic (asymptomatic group)and 45 with symptomatic(symptomatic group ). Their endocervical specimens were testedfor Chlamydia trachomatis, Neisseria gonorrhoeae by PCR, the levels of TNF-αandIL-1βby ELISA. Serum progesterone (P) and estradiol(E2) levels were measured by radioimmunoassay (RIA). The results were evaluated by SPSS for Windows (version 12.0) usingstatistical analysis.
Results Chlamydia trachomatis have no relationgnship with female asymptomaticgonococcal infections. However, the relationship between the decreased levels of TNF-α、IL-1βand the increased levels of progesterone was considered statistical significant at P＜0.05.
Conclusion Progesterone may play a key role in female less symptomatic gonococcalinfections by down-regulatd inflammatory response.
PartⅢEffect and mechanism of progesterone on PMNinflammatory responses to wild-type gonococci in vitro
Objective We used 3 types of strains associated with female symptomatic Infections and 3with asymptomatic Infections to investigate the modulation effects of progesterone on PMNinflammatory responses to gonoccocus.
Methods PMNs were isolated from Heparinized peripheral blood from healthy volunteers.After incubation of PMNs With 50 ng/mL 17β-estradiol for 6 hours at 37℃with 5% CO2,PR mRNA expression was determined by RT-PCR and immunofluorescence. Additionallythe effect of progesterone on N. gonorrhoeae-challenged polymorphonuclear leukocytesinflammatory responses at various time points were assayed by real-time RT-PCR. Akt,p-Akt (Ser473), iNOS and eNOS were detected respectively by Western blot.
Results Among these non-unique multiple isolates from asymptomatic women(ST2951,ST735 and ST436) and from symptomatic women(ST809,ST369 and ST2948) we found nosignificant difference in Ngo-PMNs inflammatory responses. In vitro PMNs infectionexperiments, progesterone suppressed expression of iNOS、TNF-α、IL-1βtranscript andiNOS protein significantly(P＜0.01) while eNOS expression revealed a slight change. Wefound that human peripheral blood PMNs did not express the classical progesteronereceptor and the role of progesterone was independent of Akt signaling pathway.Conclusions Gonococci are susceptible to progesterone or their downstream effects invitro. Progesterone induced down-regulated expression of pro-inflammatory cytokines suchas iNOS etc., which is independent of akt signaling pathway in Ngo challanged PMNs.
PartⅣEffect of progesterone on gonococci-induced apoptosisand respiratory burst of human polymorphonuclear leucocytesin vitro
Objective To investigate the regulatory effect of progesterone on apoptosis and oxidativeburst activity of polymorphonuclear leucocytes(PMNs) challenged by Neisseriagonorrhoeae (Ngo) in vitro.
Methods Isolated PMNs were incubated with progesterone or staurosporine. Staurosporinewas used as a positive control for our vitro model. Expression levels of inhibitory apoptosisproteins (IAPs), cellular IAP2(cIAP2) and X-linked IAP (XIAP) were determined byreal-time PCR. Additionally, PMNs apoptosis at various time points (3, 8, 12 and 24h) wereassayed by flow cytometry. Luminol amplified chemiluminescence methods were used toquantify the oxidative burst function of PMNs challenged with Ngo ST2951.
Results cIAP2 was up-regulated significantly in PMNs with progesterone treatment in 3hand XIAP was up-regulated slightly compared to the medium+ST2951 group, while cIAP2was down-regulated in staurosporine-challenged PMNs. Additionally we foundprogesterone delayed the onset of apoptosis activity in Ngo ST2951 challenged PMNs,notably at 12h. No statistically significant changes in PMNs oxidative burst activity wereobserved at 10 ng/mL level of progesterone. Staurosporine enhanced the production ofsuperoxide anion (respiratory burst) of human PMNs stimulated by Ngo.
Conclusion Progesterone plays an important regulatory role in the interaction of PMNs andNgo. Delayed PMNs apoptosis induced by progesterone presumably acts as a mechanismfor Ngo to avoid the innate immune response and establish long-term, low-level infection inthe female reproductive tract.
引文
1 Miles K, Churchward CP, McAuliffe L, et al. Identification and differentiation of European and African/Australian strains of Mycoplasma mycoides subspecies mycoides small-colony type using polymerase chain reaction analysis. J Vet Diagn Invest JT - Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc, 2006,18(2):168-71.
2 Bingen E, Barc MC, Brahimi N, et al. Randomly amplified polymorphic DNA analysis provides rapid differentiation of methicillin-resistant coagulase-negative staphylococcus bacteremia isolates in pediatric hospital. J Clin Microbiol JT-Journal of clinical microbiology, 1995,33(6): 1657-9.
3 Low N, Broutet N, Adu-Sarkodie Y, et al. Global control of sexually transmitted infections. Lancet, 2006, 368: 2001-2016.
4 Bozicevic I, Fenton KA, Martin IM, et al. Epidemiological correlates of asymptomatic gonorrhea. Sex Transm Dis, 2006, 33: 289-295.
5 Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect, 1999, 75: 3-17.
6 Hamilton HL, Dillard JP. Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination. Mol Microbiol JT- Molecular microbiology,2006,59(2):376-85.
7 Cloud-Hansen KA, Hackett KT, Garcia DL, et al. Neisseria gonorrhoeae uses two lytic transglycosylases to produce cytotoxic peptidoglycan monomers. J Bacteriol, 2008,190: 5989-5994.
8 Hamilton HL, Dominguez NM, Schwartz KJ, et al. Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system. Mol Microbiol JT -Molecular microbiology, 2005,55(6):1704-21.
9 Dillard JP, Seifert HS. A variable genetic island specific for Neisseria gonorrhoeae is involved in providing DNA for natural transformation and is found more often in disseminated infection isolates. Mol Microbiol JT-Molecular microbiology,2001,41(1): 263-77.
10 Martin IM, Ison CA, Aanensen DM, et al. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis JT - The Journal of infectious diseases, 2004,189(8):1497-505.
11 O'Rourke M, Ison CA, Renton AM, et al. Opa-typing: a high-resolution tool for studying the epidemiology of gonorrhoea. Mol Microbiol JT - Molecular microbiology,1995,17(5):865-75.
12 Aydin D, Koksalan K, Komec S, et al. Auxo-, sero-, and opa-typing of Neisseria gonorrhoeae strains isolated in Istanbul, Turkey. Sex Transm Dis JT - Sexually transmitted diseases, 2004,31(10):628-30.
13 Kolader ME, Dukers NH, van der Bij AK, et al. Molecular epidemiology of Neisseria gonorrhoeae in Amsterdam, The Netherlands, shows distinct heterosexual and homosexual networks. J Clin Microbiol JT - Journal of clinical microbiology,2006,44(8):2689-97.
14 Spratt BG. Multilocus sequence typing: molecular typing of bacterial pathogens in an era of rapid DNA sequencing and the internet. Curr Opin Microbiol JT - Current opinion in microbiology, 1999,2(3):312-6.
15 Viscidi RP, Demma JC, Gu J, et al. Comparison of sequencing of the por gene and typing of the opa gene for discrimination of Neisseria gonorrhoeae strains from sexual contacts. J Clin Microbiol JT - Journal of clinical microbiology, 2000,38(12):4430-8.
16 Martin IM, Ison CA, Aanensen DM, et al. Changing epidemiologic profile of quinolone-resistant Neisseria gonorrhoeae in London. J Infect Dis JT-The Journal of infectious diseases, 2005,192(7):1191-5.
17 A. K. MORRIS~(al), H. M. PALMER~(a2 c1) and H. YOUNG~(a2) Opa-typing can identify epidemiologically distinct subgroups within Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST)clusters. Epidemiology and Infection. Published online by Cambridge University Press 31May 2007
1 Folch C, Esteve A, Sanclemente C, et al. Prevalence of human immunodeficiency virus, Chlamydia trachomatis, and Neisseria gonorrhoeae and risk factors for sexually transmitted infections among immigrant female sex workers in Catalonia,Spain. Sex Transm Dis, 2008, 35:178-183.
2 Gretton S, Patrizio C, Young H. The sac-4 gene of Neisseria gonorrhoeae correlates with gonococcal subtype not co-existing chlamydial infection. Int J STD AIDS,2002,13: 174-177.
3 Edwards JL, Apicella MA. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin Microbiol Rev, 2004,17: 965-981
4 Hook, E. W., ?, and H. H. Handsfield. 1999. Gonococcal infections in the adult, p.451-466. In K. K. Holmes, P.-A. Ma 皉dh, P. F. Sparling, S. M.Lemon, W. E. Stamm,P. Piot, and J. N. Wasserheit (ed.), Sexually transmitted diseases, 3rd ed.McGraw-Hill, New York, N.Y.
5 Harvey, H. A., D. M. B. Post, and M. A. Apicella. 2002. Immortalization of human urethral epithelial cells: a model for the study of the pathogenesis of and the inflammatory cytokine response to Neisseria gonorrhoeae infection. Infect. Immun.70:5808-5815.
6 Ng LK, Martin IE. The laboratory diagnosis of Neisseria gonorrhoeae. Can J Infect Dis Med Microbiol, 2005,16:15-25.
7 Martin DH, Cammarata C, Van Der Pol B, et al. Multicenter evaluation of AMPLICOR and automated COBAS AMPLICOR CT/NG tests for Neisseria gonorrhoeae. J Clin Microbiol, 2000,38: 3544-3549.
8 Lum G, Freeman K, Nguyen NL, et al. A cluster of culture positive gonococcal infections but with false negative cppB gene based PCR. Sex Transm Infect, 2005,81: 400-402.
9 Farrell DJ, Sheedy TJ. Urinary screening for Neisseria gonorrhoeae in asymptomatic individuals from Queensland, Australia: an evaluation using three nucleic acid amplification methods. Pathology, 2001, 33: 204-205.
10 Morris AK, Palmer HM, Young H. Opa-typing can identify epidemiologically distinct subgroups within Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST) clusters. Epidemiol Infect, 2008,136: 417-420.
11 Schabereiter-Gurtner C, Hufnagl P, Sonvilla G, et al. Evaluation of a novel internally controlled real-time PCR assay targeting the 16S rRNA gene for confirmation of Neisseria gonorrhoeae infections. Clin Microbiol Infect, 2008, 14:480-486.
12 Whiley DM, Buda PJ, Bayliss J, et al. A new confirmatory Neisseria gonorrhoeae real-time PCR assay targeting the porA pseudogene. Eur J Clin Microbiol Infect Dis,2004, 23: 705-710.
13 Bruisten SM, Noordhoek GT, van den Brule AJ, et al. Multicenter validation of the cppB gene as a PCR target for detection of Neisseria gonorrhoeae. J Clin Microbiol,2004, 42: 4332-4334.
14 Bae BH, Amin RM, Korzis J. Detection of L-forms of Neisseria gonorrhoeae in pure and mixed culture suspensions by an enzyme immunoassay. Am J Clin Pathol,1986, 85: 618-622.
15 Folch C, Esteve A, Sanclemente C, et al. Prevalence of human immunodeficiency virus, Chlamydia trachomatis, and Neisseria gonorrhoeae and risk factors for sexually transmitted infections among immigrant female sex workers in Catalonia,Spain. Sex Transm Dis, 2008, 35:178-183.
16 Gretton S, Patrizio C, Young H. The sac-4 gene of Neisseria gonorrhoeae correlates with gonococcal subtype not co-existing chlamydial infection. Int J STD AIDS,2002,13: 174-177.
17 Kaushic C, Zhou F, Murdin AD, et al. Effects of estradiol and progesterone on susceptibility and early immune responses to Chlamydia trachomatis infection in the female reproductive tract. Infect Immun, 2000, 68: 4207-4216.
18 Marx SG, Wentz MJ, Mackay LB, et al. Effects of progesterone on iNOS, COX-2,and collagen expression in the cervix. J Histochem Cytochem, 2006, 54: 623-639.
19 Kalo-Klein, A., and S.S. Witkin. Candida albicans: Cellular immune system interactions during different stages of the menstrual cycle. Am J Obstet Gynecol,1989,161: 1132-1136.
20 MacDonald EM, Savoy A, Gillgrass A, et al. Susceptibility of human female primary genital epithelial cells to herpes simplex virus, type-2 and the effect of TLR3 ligand and sex hormones on infection. Biol Reprod, 2007, 77:1049-1059.
21 Patrone JB, Bish SE, Stein DC. TNF-alpha-independent IL-8 expression: alterations in bacterial challenge dose cause differential human monocytic cytokine response. J Immunol, 2006,177:1314-1322.
22 Maisey K, Nardocci G, Imarai M, et al. Expression of proinflammatory cytokines and receptors by human fallopian tubes in organ culture following challenge with Neisseria gonorrhoeae. Infect Immun, 2003,71: 527-532.
23 Rarick M, McPheeters C, Bright S, et al. Evidence for cross-regulated cytokine response in human peripheral blood mononuclear cells exposed to whole gonococcal bacteria in vitro. Microb Pathog, 2006, 40: 261-270.
1. Peeling RW, Mabey D, Herring A, Hook EW 3rd. Why do we need quality -assured diagnostic tests for sexually transmitted infections? Nat Rev Microbiol. 2006 Dec;4(12):909-921. Review.
2. Patrone JB, Bish SE, Stein DC. TNF-alpha-independent IL-8 expression: alterations in bacterial challenge dose cause differential human monocytic cytokine response. J Immunol, 2006,177:1314-1322.
3. Maisey K, Nardocci G, Imarai M, et al. Expression of proinflammatory cytokines and receptors by human fallopian tubes in organ culture following challenge with Neisseria gonorrhoeae. Infect Immun, 2003,71: 527-532.
4. Rarick M, McPheeters C, Bright S, et al. Evidence for cross-regulated cytokine response in human peripheral blood mononuclear cells exposed to whole gonococcal bacteria in vitro. Microb Pathog, 2006, 40: 261-270.
5. Nathan CF,Xie O.Nitric oxide synthases:roles,tolls,and controls. Cell.l994;70(5):915
6. Van Dervort AL,Yan L,Mandara PJ,et al.ntric oxide regulates endotoxin-induced TNF-production by human neutrophils. J Immunol, 1994;152(ll);4102
7. Householder TC, Fozo EM, Cardinale JA et al. Gonococcal nitric oxide reductase is encoded by a single gene, norB, which is required for anaerobic growth and is induced by nitric oxide. Infect Immun 2000; 68:5241-5246.
8. Edwards JL, Apicella MA. Neisseria gonorrhoeae PLD directly interacts with Akt kinase upon infection of primary, human, cervical epithelial cells. Cell Microbiol. 2006 Aug;8(8):1253-1271.
9. Jung CH, Jung H, Shin YC, Park JH, Jun CY, Kim HM, Yim HS, Shin MG, Bae HS,Kim SH, Ko SG. Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophage. J Ethnopharmacol. 2007 Aug 15;113(1):183-187.
10. Kim MP, Park SI, Kopetz S, et al. Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis. Cell Tissue Res, 2009, 335:249-259.
11. Ballare C, Vallejo G, Vicent GP, et al. Progesterone signaling in breast and endometrium. J Steroid Biochem Mol Biol, 2006,102: 2-10.
12. Snyder LA, Butcher SA, Saunders NJ. Comparative whole-genome analyses reveal over 100 putative phase-variable genes in the pathogenic Neisseria spp. Microbiology 2001;147(Pt 8):2321-2332.
13. Dehio C, Gray-Owen SD, Meyer TF. Host cell invasion by pathogenic Neisseriae. Subcell Biochem 2000;33:61-96.
14. Jerse AE, Cohen MS, Drown PM, et al. Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. J Exp Med 1994;179(3):911-920.
15. Burch CL, Danaher RJ, Stein DC. Antigenic variation in Neisseria gonorrhoeae:production of multiple lipooligosaccharides. J Bacteriol 1997;179(3):982-986.
16. Aerts JL, Christiaens MR, Vandekerckhove P. Evaluation of progesterone receptor expression in eosinophils using real-time quantitative PCR. Biochim Biophys Acta 2002;1571(3):167-172.
17. Cutolo M, Sulli A, Capellino S, et al. Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 2004;13(9):635-638.
18. Kaushic C, Ashkar AA, Reid LA, Rosenthal KL. Progesterone increases susceptibility and decreases immune responses to genital herpes infection. J Virol 2003;77(8):4558-4565.
19. Brooks-Asplund EM, Tupper CE, Daun JM, Kenney WL, Cannon JG. Hormonal modulation of interleukin-6, tumor necrosis factor and associated receptor secretion in postmenopausal women. Cytokine 2002; 19(4): 193-200.
20. Kaushic C, Zhou F, Murdin AD, Wira CR. Effects of estradiol and progesterone on susceptibility and early immune responses to Chlamydia trachomatis infection in the female reproductive tract. Infect Immun 2000;68(7):4207-4216.
21. MacDonald EM, Savoy A, Gillgrass A, et al. Susceptibility of human female primary genital epithelial cells to herpes simplex virus, type-2 and the effect of TLR3 ligand and sex hormones on infection. Biol Reprod, 2007, 77:1049-1059.
22. Fidel PL, Jr., Cutright J, Steele C. Effects of reproductive hormones on experimental vaginal candidiasis. Infect Immun 2000;68(2):651-657.
23. Hedges SR, Mayo MS, Mestecky J, Hook EW, III, Russell MW. Limited local and systemic antibody responses to Neisseria gonorrhoeae during uncomplicated genital infections. Infect Immun 1999; 67(8):3937-3946.
1 Bozicevic I, Fenton KA, Martin IM, Rudd EA, Ison CA, Nanchahal K, Wellings K.Epidemiological Correlates of Asymptomatic Gonorrhea. Sexually Transmitted Diseases, 2006; 33(5): 289-295
2 Molloy EJ, O'Neill AJ, Grantham JJ, Sheridan-Pereira M, Fitzpatrick JM, Webb DW,Watson RW. Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone. Blood. 2003 Oct 1;102(7):2653-9.
3 Roos D, van Bruggen R, Meischl C. Oxidative killing of microbes by neutrophils.Microbes and infection / Institut Pasteur 2003; 5:1307-1315.
4 Kobayashi SD, Voyich JM, Somerville GA, Braughton KR, Malech HL, Musser JM,DeLeo FR. An apoptosis-differentiation program in human polymorphonuclear leukocytes facilitates resolution of inflammation. Journal of leukocyte biology 2003;73:315-322.
5 Simons MP, Nauseef WM, Griffith TS, Apicella MA. Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear leukocytes. Cellular microbiology 2006;8:1780-1790.
6 祁文瑾，石一复，妊娠与念珠菌性外阴阴道炎，国外医学妇幼保健分。2003，14(6)343—345
7 Watson RW, O'Neill A, Brannigen AE, et al. Regulation of Fas antibody induced neutrophil apoptosis is both caspase and mitochondrial dependent.FEBS Lett. 1999;453:67-71.
8 TibbettsTA, Conneely OM, O'Malley BW. Progesterone via its receptor antagonizes the pro-inflammatory activity of estrogen in the mouse uterus. Biol Reprod.1999;60:1158-1165.
9 Yaffe K, Sawaya G, Lieberburg I,et al. Estrogen therapy in postmanopaul women:effects on cognitive function and dementia. JAMA, 1998, 279(9):688-695
10 White RF, Darkow DJ,Lang JL. Estrogen relaxes coronary arteries by opening BKCa channels through a cGMP-dependent mechanism. Circ Res,1995, 77:936-942
11 Tao J, Liu YQ, Li Y, Peng JL, Li L, Liu J, Shen X, Shen GX, Tu YT. Hypoxia: dual effect on the expression of transferrin receptor in human melanoma A375 cell line.Experimental dermatology 2007; 16:899-904.
12 D.A. Shear,R. Galani,S.W. Hoffman,D.G.Stein,progesterone protect agsinst necrotic damage and behaviroral abnomalities caused by traumatic brain injury,Exp.Neurol.l78(2002))59-67
13 Labombarda F,GonzaleZ SL,Gonzalez DM, Guennoun R,Schumacher M,de Nicola AF(2002) Cellular basis for progesterone neuroprotection in the injured spinal cord. J Neutrotrauma 19:343-355
14 Dai D,Wolf DM,Litman ES,et al.Progesterone inhibits human endometrial carcinoma cell growth and invasiveness:down-regulation of cellular adhesion molecules through progesterone B receptors.Cancer Res, 2002, 62(3): 881-886.
15 Nusbaum P, Laine C, Seveau S, Lesavre P, Halbwachs-Mecarelli L. Early membrane events in polymorphonuclear cell (PMN) apoptosis: membrane blebbing and vesicle release, CD43 and CD16 down-regulation and phosphatidylserine externalization. Biochemical Society transactions 2004; 32:477-479.
16 Davis BH, Olsen SH, Ahmad E, Bigelow NC. Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients. Archives of pathology &laboratory medicine 2006; 130:654-661.
17 Schroder AK, Uciechowski P, Fleischer D, Rink L. Crosslinking of CD66B on peripheral blood neutrophils mediates the release of interleukin-8 from intracellular storage. Human immunology 2006; 67:676-682.
18 Simons MP, Nauseef WM, Apicella MA. Interactions of Neisseria gonorrhoeae with adherent polymorphonuclear leukocytes. Infection and immunity 2005; 73:1971-1977.
19 Hasegawa T, Suzuki K, Sakamoto C, Ohta K, Nishiki S, Hino M, Tatsumi N, Kitagawa S. Expression of the inhibitor of apoptosis (LAP) family members in human neutrophils:up-regulation of cIAP2 by granulocyte colony-stimulating factor and overexpression of cIAP2 in chronic neutrophilic leukemia. Blood 2003; 101:1164-1171.
20 Cui X, Imaizumi T, Yoshida H, Tanji K, Matsumiya T, Satoh K. Lipopolysaccharide induces the expression of cellular inhibitor of apoptosis protein-2 in human macrophages. Biochimica et biophysica acta 2000; 1524:178-182.
21 Stehlik C, de Martin R, Binder BR, Lipp J. Cytokine induced expression of porcine inhibitor of apoptosis protein (iap) family member is regulated by NF-kappa B.Biochemical and biophysical research communications 1998; 243:827-832.
22 Chu ZL, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW. Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis C-IAP2 is under NF-kappaB control. Proceedings of the National Academy of Sciences of the United States of America 1997; 94:10057-10062.
23 Hawkins JV, Emmel EL, Feuer JJ, Nedelman MA, Harvey CJ, IGein HJ, Rozmiarek H,Kennedy AR, Lichtenstein GR, Billings PC. Protease activity in a hapten-induced model of ulcerative colitis in rats. Digestive diseases and sciences 1997;42:1969-1980.
1. Low N, Broutet N, Adu-Sarkodie Y, et al. Global control of sexually transmitted infections. Lancet, 2006, 368: 2001-2016.
2. Bozicevic I, Fenton KA, Martin IM, et al. Epidemiological correlates of asymptomatic gonorrhea. Sex Transm Dis, 2006, 33: 289-295.
3. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect, 1999, 75: 3-17.
4. Edwards JL, Apicella MA. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin Microbiol Rev,2004,17: 965-981, table of contents.
5. Rudel T, Scheurerpflug I, Meyer TF. Neisseria PilC protein identified as type-4 pilus tip-located adhesin. Nature, 1995, 373: 357-359.
6. Gulati S, Cox A, Lewis LA, et al. Enhanced factor H binding to sialylated Gonococci is restricted to the sialylated lacto-N-neotetraose lipooligosaccharide species: implications for serum resistance and evidence for a bifunctional lipooligosaccharide sialyltransferase in Gonococci. Infect Immun JT- Infection and immunity,2005,73(ll):7390-7.
7. Ram S, McQuillen DP, Gulati S, et al. Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. J Exp Med JT - The Journal of experimental medicine,1998,188(4):671-80.
8. Nowicki S, Ram P, Pham T, et al. Pelvic inflammatory disease isolates of Neisseria gonorrhoeae are distinguished by Clq-dependent virulence for newborn rats and by the sac-4 region. Infect Immun JT - Infection and immunity, 1997,65(6):2094-9.
9. Hamilton HL, Dillard JP.Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination. Mol Microbiol. 2006 Jan;59(2):376-85.
10. Harvey HA, Jennings MP, Campbell CA, et al. Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol Microbiol, 2001, 42: 659-672.
11. Kuhlewein C, Rechner C, Meyer TF, et al. Low - phosphate-dependent invasion resembles a general way for Neisseria gonorrhoeae to enter host cells. Infect Immun, 2006, 74: 4266-4273.
12. Pils S, Gerrard DT, Meyer A, et al. CEACAM3: an innate immune receptor directed against human-restricted bacterial pathogens. Int J Med Microbiol, 2008, 298:553-560.
13. Stocks, S. C, M. A. Kerr, C. Haslett, and I. Dransfield. 1995. CD66-de-pendent neutrophil activation: a possible mechanism for vascular selectin-mediated regulation of neutrophil adhesion. J. Leukoc. Biol. 58:40-48.
14. Schmitter, T., F. Agerer, L. Peterson, P. Munzner, and C. R. Hauck. 2004.Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific patho-gens. J. Exp. Med.199:35-46.
15. Timmerman MM, Shao JQ, Apicella MA. Ultrastructural analysis of the pathogenesis of Neisseria gonorrhoeae endometrial infection. Cell Microbiol, 2005, 7: 627-636.
16. Edwards JL, Apicella MA. Neisseria gonorrhoeae PLD directly interacts with Akt kinase upon infection of primary, human, cervical epithelial cells. Cell Microbiol,2006, 8: 1253-1271.
17. Marcinkiweicz J. Neutrophil chloramines: missing links between innate and acquired immunity[J]. Immunol Today, 1997,18: 577
18. S G Casey, W M Shafer, and J K Spitznagel. Neisseria gonorrhoeae survive intraleukocytic oxygen-independent antimicrobial capacities of anaerobic and aerobic granulocytes in the presence of pyocin lethal for extracellular gonococci. Infect Immun. 1986 May; 52(2): 384-389.
19. Quinn K, Henriques M, Parker T, et al. Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases. Am J Physiol Heart Circ Physiol,2008, 295: H1817-1824.
20. Bjerknes, R., H.-K. Guttormsen, C. O. Solberg, and L. M. Wetzler. 1995. Neisserial porins inhibit human neutrophil actin polymerization, degranu-lation, opsonin receptor expression, and phagocytosis but prime the neu-trophils to increase their oxidative burst. Infect. Immun. 63:160-167.
21. Lorenzen, D. R., D. Gunther, J. Pandit, T. Rudel, E. Brandt, and T. F. Meyer. 2000.Neisseria gonorrhoeae porin modifies the oxidative burst of human professional phagocytes. Infect. Immun. 68:6215-6222.
22. Lorenzen, D. R., D. Gunther, J. Pandit, T. Rudel, E. Brandt, and T. F.Meyer. 2000.Neisseria gonorrhoeae porin modifies the oxidative burst of human professional phagocytes. Infect. Immun. 68:6215-6222.
23. Hampton, M. B., A. J. Kettle, and C. C. Winterbourn. 1998. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92:3007-3017.
24. S R Johnson, B M Steiner, D D Cruce, G H Perkins, and R J Arko. Characterization of a catalase-deficient strain of Neisseria gonorrhoeae: evidence for the significance of catalase in the biology of N. gonorrhoeae. Infect Immun. 1993 April; 61(4):1232-1238.
25. Karen H. L. Lim,l Christopher E. Jones,l Rachel N. vanden Hoven,l Jennifer L.Edwards, Megan L. Falsetta, Michael A. Apicella, Michael P. Jennings, and Alastair G. McEwanl. Metal Binding Specificity of the MntABC Permease of Neisseria gonorrhoeae and Its Influence on Bacterial Growth and Interaction with Cervical Epithelial Cells. Infect Immun. 2008 August; 76(8): 3569-3576.
26. Kate L. Seib, Hsing-Ju Wu,Stephen P. Kidd, Michael A. Apicella, Michael P.Jennings,and Alastair G. McEwan. Defenses against Oxidative Stress in Neisseria gonorrhoeae: a System Tailored for a Challenging Environment. Microbiology and Molecular Biology Reviews, June 2006;70(2): 344-361
27. Susan Turner, Eleanor Reid, Harry Smith, and Jeffrey Cole. A novel cytochrome c peroxidase from Neisseria gonorrhoeae: a lipoprotein from a Gram-negative bacterium. Biochem J. 2003 August 1; 373(Pt 3): 865-873.
28. Seib, K. L., M. P. Jennings, and A. G McEwan. 2003. A Sco homologue plays a role in defense against oxidative stress in pathogenic Neisseria. FEBS Letters, Volume 546, Issue 2, Pages 411-415
29. Rest, R. F., J. Liu, R. Talukdar, J. V. Frangipane, and D. Simon. 1994. Interaction of pathogenic Neisseria with host defenses. What happens in vivo? Ann. N. Y. Acad. Sci.730:182-196.
30. ohannsen DB Johnston DM,Koymen HO , et al . A Neisseria gonorrhoeae immunoglobulin Al protease mutant is infectious in the human challenge model of urethral infection. [J]Infec Immun , 1999 ,67 (6):3009-3013.
31. Masri HP, Cornelissen CN. Specific Ligand Binding Attributable to Individual Epitopes of Gonococcal Transferrin Binding Protein A. [J ] . Infect Immun , 2002 ,70(2) :732-740
32. Lin L, Ayala P, Larson J, Mulks M, Fukuda M, Carlsson SR, Enns C, So M. The Neisseria type 2 IgAl protease cleaves LAMPl and promotes survival of bacteria within epithelial cells. Mol Microbiol. 1997 Jun;24(5):1083-94.
33. K(?) llstrom H , Islam MS , Berggren PO ,et al. Cell signaling by the type IV P I li of pathogenic neisseria. J Biol Chem, 1998 ,273(34):21777-21782.
34. Rudel T , Schmid A , Benz R , et al . Modulation of neisseria porin(PorB) by cytosolic ATP/ GTP of target cells : parallels between pathogen accommodation and mitochondrial endosymbiosis. Cell,1996,85(3): 391-402.
35. Ayala P , Vasquez B , Wetzler L ,et al . Neisseria gonorrhoeae porin P1.B induces endosome exocytosis and a redistribution of Iampl to the plasma membrane. Infection and Immunity ,2002 ,70 (11): 5965-5971.
36. Cauci S, Culhane JF. Modulation of vaginal immune response among pregnant women with bacterial vaginosis by Trichomonas vaginalis, Chlamydia trachomatis,Neisseria gonorrhoeae, and yeast. Am J Obstet Gynecol, 2007,196:133 el31-137.
37. van Ulsen P,Tommassen J. Protein secretion and secreted proteins in pathogenic Neisseriaceae. FEMS Microbiol Rev, 2006, 30: 292-319.
38. Derocco AJ, Yost-Daljev MK, Kenney CD, et al. Kinetic analysis of ligand interaction with the gonococcal transferrin-iron acquisition system. Biometals, 2008 Dec 2.
39. Biswas, G D : Anderson, J E : Sparling, P F. Cloning and functional characterization of Neisseria gonorrhoeae tonB, exbB and exbD genes. Mol-Microbiol. 1997 Apr;24(1): 169-79
40. Ronpirin C,Jerse AE,Cornelissen CN.Gonococcal Genes Encoding Transferrin-Binding Proteins A and B Are Arranged in a Bicistronic Operon but Are Subject to Differential Expression.[J]Infect Immun,2001,69(10):6336-6347.
41. Viscidi RP, Demma JC, Gu J, et al. Comparison of sequencing of the por gene and typing of the opa gene for discrimination of Neisseria gonorrhoeae strains from sexual contacts. J Clin Microbiol JT - Journal of clinical microbiology,2000,38(12):4430-8.
42. Jennifer M. Noto and Cynthia Nau Cornelissen. Identification of TbpA Residues Required for Transferrin-Iron Utilization by Neisseria gonorrhoeae. Infect Immun.2008 May; 76(5): 1960-1969.
43. Frangipane, J. V., and Rest, R. F. Anaerobic growth and cytidine 5'-monophospho-N-acetylneuraminic acid act synergistically to induce high-level serum resistance in Neisseria gonorrhoeae. (1993) Infect. Immun. 61,1657-1666.
44. G T Hoehn and V L Clark. Isolation and Nucleotide Sequence of the Gene (aniA)Encoding the Major Anaerobically Induced Outer Membrane Protein of Neisseria gonorrhoeae. Infect Immun. 1992 November; 60(11): 4695-4703.
45. Boulanger,M. J., andMurphy,M. E. P. Crystal structure of the soluble domain of the major anaerobically induced outer membrane protein (AniA) from pathogenic Neisseria: a new class of copper-containing nitrite reductases. (2002) J.Mol. Biol.315,1111-1127
46. Clark, V. L., Campbell, L. A., Palermo, D. A., Evans, T. M., and Klimpel,K.W.Induction and repression of outer membrane proteins by anaerobic growth of Neisseria gonorrhoeae. (1987) Infect. Immun. 55,1359-1364
47. Overton Tim W; Whitehead Rebekah; Li Ying; Snyder Lori A S; Saunders Nigel J;Smith Harry; Cole Jeff A. Coordinated Regulation of the Neisseria gonorrhoeae-truncated Denitrification Pathway by the Nitric Oxide-sensitive Repressor,NsrR, and Nitrite-insensitive NarQ-NarP. The Journal of biological chemistry 2006;281(44):33115-26.
48. Cardinale, J. A., and Clark, V. L. Expression of AniA, the Major Anaerobically Induced Outer Membrane Protein of Neisseria gonorrhoeae, Provides Protection against Killing by Normal Human Sera. (2000) Infect. Immun. 68, 4368-4369
49. Jean A. Cardinale and Virginia L. Clark. Determinants of nitric oxide steady-state levels during anaerobic respiration by Neisseria gonorrhoeae. Molecular Microbiology (2005) 58(1), 177-188
50. Potter AJ, Kidd SP, Edwards JL, et al. Thioredoxin reductase is essential for protection of Neisseria gonorrhoeae against killing by nitric oxide and for bacterial growth during interaction with cervical epithelial cells. J Infect Dis, 2009, 199:227-235.
51. Isabella V, Wright LF, Barth K, et al. cis- and trans-acting elements involved in regulation of norB (norZ), the gene encoding nitric oxide reductase in Neisseria gonorrhoeae. Microbiology, 2008,154: 226-239.
52. Ku SC, Schulz BL, Power PM, et al. The pilin O-glycosylation pathway of pathogenic Neisseria is a general system that glycosylates AniA, an outer membrane nitrite reductase. Biochem Biophys Res Commun, 2009, 378: 84-89.
2 Bingen E, Barc MC, Brahimi N, et al. Randomly amplified polymorphic DNA analysis provides rapid differentiation of methicillin-resistant coagulase-negative staphylococcus bacteremia isolates in pediatric hospital. J Clin Microbiol JT-Journal of clinical microbiology, 1995,33(6): 1657-9.
3 Low N, Broutet N, Adu-Sarkodie Y, et al. Global control of sexually transmitted infections. Lancet, 2006, 368: 2001-2016.
4 Bozicevic I, Fenton KA, Martin IM, et al. Epidemiological correlates of asymptomatic gonorrhea. Sex Transm Dis, 2006, 33: 289-295.
5 Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect, 1999, 75: 3-17.
6 Hamilton HL, Dillard JP. Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination. Mol Microbiol JT- Molecular microbiology,2006,59(2):376-85.
7 Cloud-Hansen KA, Hackett KT, Garcia DL, et al. Neisseria gonorrhoeae uses two lytic transglycosylases to produce cytotoxic peptidoglycan monomers. J Bacteriol, 2008,190: 5989-5994.
8 Hamilton HL, Dominguez NM, Schwartz KJ, et al. Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system. Mol Microbiol JT -Molecular microbiology, 2005,55(6):1704-21.
9 Dillard JP, Seifert HS. A variable genetic island specific for Neisseria gonorrhoeae is involved in providing DNA for natural transformation and is found more often in disseminated infection isolates. Mol Microbiol JT-Molecular microbiology,2001,41(1): 263-77.
10 Martin IM, Ison CA, Aanensen DM, et al. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis JT - The Journal of infectious diseases, 2004,189(8):1497-505.
11 O'Rourke M, Ison CA, Renton AM, et al. Opa-typing: a high-resolution tool for studying the epidemiology of gonorrhoea. Mol Microbiol JT - Molecular microbiology,1995,17(5):865-75.
12 Aydin D, Koksalan K, Komec S, et al. Auxo-, sero-, and opa-typing of Neisseria gonorrhoeae strains isolated in Istanbul, Turkey. Sex Transm Dis JT - Sexually transmitted diseases, 2004,31(10):628-30.
13 Kolader ME, Dukers NH, van der Bij AK, et al. Molecular epidemiology of Neisseria gonorrhoeae in Amsterdam, The Netherlands, shows distinct heterosexual and homosexual networks. J Clin Microbiol JT - Journal of clinical microbiology,2006,44(8):2689-97.
14 Spratt BG. Multilocus sequence typing: molecular typing of bacterial pathogens in an era of rapid DNA sequencing and the internet. Curr Opin Microbiol JT - Current opinion in microbiology, 1999,2(3):312-6.
15 Viscidi RP, Demma JC, Gu J, et al. Comparison of sequencing of the por gene and typing of the opa gene for discrimination of Neisseria gonorrhoeae strains from sexual contacts. J Clin Microbiol JT - Journal of clinical microbiology, 2000,38(12):4430-8.
16 Martin IM, Ison CA, Aanensen DM, et al. Changing epidemiologic profile of quinolone-resistant Neisseria gonorrhoeae in London. J Infect Dis JT-The Journal of infectious diseases, 2005,192(7):1191-5.
17 A. K. MORRIS~(al), H. M. PALMER~(a2 c1) and H. YOUNG~(a2) Opa-typing can identify epidemiologically distinct subgroups within Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST)clusters. Epidemiology and Infection. Published online by Cambridge University Press 31May 2007
1 Folch C, Esteve A, Sanclemente C, et al. Prevalence of human immunodeficiency virus, Chlamydia trachomatis, and Neisseria gonorrhoeae and risk factors for sexually transmitted infections among immigrant female sex workers in Catalonia,Spain. Sex Transm Dis, 2008, 35:178-183.
2 Gretton S, Patrizio C, Young H. The sac-4 gene of Neisseria gonorrhoeae correlates with gonococcal subtype not co-existing chlamydial infection. Int J STD AIDS,2002,13: 174-177.
3 Edwards JL, Apicella MA. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin Microbiol Rev, 2004,17: 965-981
4 Hook, E. W., ?, and H. H. Handsfield. 1999. Gonococcal infections in the adult, p.451-466. In K. K. Holmes, P.-A. Ma 皉dh, P. F. Sparling, S. M.Lemon, W. E. Stamm,P. Piot, and J. N. Wasserheit (ed.), Sexually transmitted diseases, 3rd ed.McGraw-Hill, New York, N.Y.
5 Harvey, H. A., D. M. B. Post, and M. A. Apicella. 2002. Immortalization of human urethral epithelial cells: a model for the study of the pathogenesis of and the inflammatory cytokine response to Neisseria gonorrhoeae infection. Infect. Immun.70:5808-5815.
6 Ng LK, Martin IE. The laboratory diagnosis of Neisseria gonorrhoeae. Can J Infect Dis Med Microbiol, 2005,16:15-25.
7 Martin DH, Cammarata C, Van Der Pol B, et al. Multicenter evaluation of AMPLICOR and automated COBAS AMPLICOR CT/NG tests for Neisseria gonorrhoeae. J Clin Microbiol, 2000,38: 3544-3549.
8 Lum G, Freeman K, Nguyen NL, et al. A cluster of culture positive gonococcal infections but with false negative cppB gene based PCR. Sex Transm Infect, 2005,81: 400-402.
9 Farrell DJ, Sheedy TJ. Urinary screening for Neisseria gonorrhoeae in asymptomatic individuals from Queensland, Australia: an evaluation using three nucleic acid amplification methods. Pathology, 2001, 33: 204-205.
10 Morris AK, Palmer HM, Young H. Opa-typing can identify epidemiologically distinct subgroups within Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST) clusters. Epidemiol Infect, 2008,136: 417-420.
11 Schabereiter-Gurtner C, Hufnagl P, Sonvilla G, et al. Evaluation of a novel internally controlled real-time PCR assay targeting the 16S rRNA gene for confirmation of Neisseria gonorrhoeae infections. Clin Microbiol Infect, 2008, 14:480-486.
12 Whiley DM, Buda PJ, Bayliss J, et al. A new confirmatory Neisseria gonorrhoeae real-time PCR assay targeting the porA pseudogene. Eur J Clin Microbiol Infect Dis,2004, 23: 705-710.
13 Bruisten SM, Noordhoek GT, van den Brule AJ, et al. Multicenter validation of the cppB gene as a PCR target for detection of Neisseria gonorrhoeae. J Clin Microbiol,2004, 42: 4332-4334.
14 Bae BH, Amin RM, Korzis J. Detection of L-forms of Neisseria gonorrhoeae in pure and mixed culture suspensions by an enzyme immunoassay. Am J Clin Pathol,1986, 85: 618-622.
15 Folch C, Esteve A, Sanclemente C, et al. Prevalence of human immunodeficiency virus, Chlamydia trachomatis, and Neisseria gonorrhoeae and risk factors for sexually transmitted infections among immigrant female sex workers in Catalonia,Spain. Sex Transm Dis, 2008, 35:178-183.
16 Gretton S, Patrizio C, Young H. The sac-4 gene of Neisseria gonorrhoeae correlates with gonococcal subtype not co-existing chlamydial infection. Int J STD AIDS,2002,13: 174-177.
17 Kaushic C, Zhou F, Murdin AD, et al. Effects of estradiol and progesterone on susceptibility and early immune responses to Chlamydia trachomatis infection in the female reproductive tract. Infect Immun, 2000, 68: 4207-4216.
18 Marx SG, Wentz MJ, Mackay LB, et al. Effects of progesterone on iNOS, COX-2,and collagen expression in the cervix. J Histochem Cytochem, 2006, 54: 623-639.
19 Kalo-Klein, A., and S.S. Witkin. Candida albicans: Cellular immune system interactions during different stages of the menstrual cycle. Am J Obstet Gynecol,1989,161: 1132-1136.
20 MacDonald EM, Savoy A, Gillgrass A, et al. Susceptibility of human female primary genital epithelial cells to herpes simplex virus, type-2 and the effect of TLR3 ligand and sex hormones on infection. Biol Reprod, 2007, 77:1049-1059.
21 Patrone JB, Bish SE, Stein DC. TNF-alpha-independent IL-8 expression: alterations in bacterial challenge dose cause differential human monocytic cytokine response. J Immunol, 2006,177:1314-1322.
22 Maisey K, Nardocci G, Imarai M, et al. Expression of proinflammatory cytokines and receptors by human fallopian tubes in organ culture following challenge with Neisseria gonorrhoeae. Infect Immun, 2003,71: 527-532.
23 Rarick M, McPheeters C, Bright S, et al. Evidence for cross-regulated cytokine response in human peripheral blood mononuclear cells exposed to whole gonococcal bacteria in vitro. Microb Pathog, 2006, 40: 261-270.
1. Peeling RW, Mabey D, Herring A, Hook EW 3rd. Why do we need quality -assured diagnostic tests for sexually transmitted infections? Nat Rev Microbiol. 2006 Dec;4(12):909-921. Review.
2. Patrone JB, Bish SE, Stein DC. TNF-alpha-independent IL-8 expression: alterations in bacterial challenge dose cause differential human monocytic cytokine response. J Immunol, 2006,177:1314-1322.
3. Maisey K, Nardocci G, Imarai M, et al. Expression of proinflammatory cytokines and receptors by human fallopian tubes in organ culture following challenge with Neisseria gonorrhoeae. Infect Immun, 2003,71: 527-532.
4. Rarick M, McPheeters C, Bright S, et al. Evidence for cross-regulated cytokine response in human peripheral blood mononuclear cells exposed to whole gonococcal bacteria in vitro. Microb Pathog, 2006, 40: 261-270.
5. Nathan CF,Xie O.Nitric oxide synthases:roles,tolls,and controls. Cell.l994;70(5):915
6. Van Dervort AL,Yan L,Mandara PJ,et al.ntric oxide regulates endotoxin-induced TNF-production by human neutrophils. J Immunol, 1994;152(ll);4102
7. Householder TC, Fozo EM, Cardinale JA et al. Gonococcal nitric oxide reductase is encoded by a single gene, norB, which is required for anaerobic growth and is induced by nitric oxide. Infect Immun 2000; 68:5241-5246.
8. Edwards JL, Apicella MA. Neisseria gonorrhoeae PLD directly interacts with Akt kinase upon infection of primary, human, cervical epithelial cells. Cell Microbiol. 2006 Aug;8(8):1253-1271.
9. Jung CH, Jung H, Shin YC, Park JH, Jun CY, Kim HM, Yim HS, Shin MG, Bae HS,Kim SH, Ko SG. Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophage. J Ethnopharmacol. 2007 Aug 15;113(1):183-187.
10. Kim MP, Park SI, Kopetz S, et al. Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis. Cell Tissue Res, 2009, 335:249-259.
11. Ballare C, Vallejo G, Vicent GP, et al. Progesterone signaling in breast and endometrium. J Steroid Biochem Mol Biol, 2006,102: 2-10.
12. Snyder LA, Butcher SA, Saunders NJ. Comparative whole-genome analyses reveal over 100 putative phase-variable genes in the pathogenic Neisseria spp. Microbiology 2001;147(Pt 8):2321-2332.
13. Dehio C, Gray-Owen SD, Meyer TF. Host cell invasion by pathogenic Neisseriae. Subcell Biochem 2000;33:61-96.
14. Jerse AE, Cohen MS, Drown PM, et al. Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. J Exp Med 1994;179(3):911-920.
15. Burch CL, Danaher RJ, Stein DC. Antigenic variation in Neisseria gonorrhoeae:production of multiple lipooligosaccharides. J Bacteriol 1997;179(3):982-986.
16. Aerts JL, Christiaens MR, Vandekerckhove P. Evaluation of progesterone receptor expression in eosinophils using real-time quantitative PCR. Biochim Biophys Acta 2002;1571(3):167-172.
17. Cutolo M, Sulli A, Capellino S, et al. Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 2004;13(9):635-638.
18. Kaushic C, Ashkar AA, Reid LA, Rosenthal KL. Progesterone increases susceptibility and decreases immune responses to genital herpes infection. J Virol 2003;77(8):4558-4565.
19. Brooks-Asplund EM, Tupper CE, Daun JM, Kenney WL, Cannon JG. Hormonal modulation of interleukin-6, tumor necrosis factor and associated receptor secretion in postmenopausal women. Cytokine 2002; 19(4): 193-200.
20. Kaushic C, Zhou F, Murdin AD, Wira CR. Effects of estradiol and progesterone on susceptibility and early immune responses to Chlamydia trachomatis infection in the female reproductive tract. Infect Immun 2000;68(7):4207-4216.
21. MacDonald EM, Savoy A, Gillgrass A, et al. Susceptibility of human female primary genital epithelial cells to herpes simplex virus, type-2 and the effect of TLR3 ligand and sex hormones on infection. Biol Reprod, 2007, 77:1049-1059.
22. Fidel PL, Jr., Cutright J, Steele C. Effects of reproductive hormones on experimental vaginal candidiasis. Infect Immun 2000;68(2):651-657.
23. Hedges SR, Mayo MS, Mestecky J, Hook EW, III, Russell MW. Limited local and systemic antibody responses to Neisseria gonorrhoeae during uncomplicated genital infections. Infect Immun 1999; 67(8):3937-3946.
1 Bozicevic I, Fenton KA, Martin IM, Rudd EA, Ison CA, Nanchahal K, Wellings K.Epidemiological Correlates of Asymptomatic Gonorrhea. Sexually Transmitted Diseases, 2006; 33(5): 289-295
2 Molloy EJ, O'Neill AJ, Grantham JJ, Sheridan-Pereira M, Fitzpatrick JM, Webb DW,Watson RW. Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone. Blood. 2003 Oct 1;102(7):2653-9.
3 Roos D, van Bruggen R, Meischl C. Oxidative killing of microbes by neutrophils.Microbes and infection / Institut Pasteur 2003; 5:1307-1315.
4 Kobayashi SD, Voyich JM, Somerville GA, Braughton KR, Malech HL, Musser JM,DeLeo FR. An apoptosis-differentiation program in human polymorphonuclear leukocytes facilitates resolution of inflammation. Journal of leukocyte biology 2003;73:315-322.
5 Simons MP, Nauseef WM, Griffith TS, Apicella MA. Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear leukocytes. Cellular microbiology 2006;8:1780-1790.
6 祁文瑾，石一复，妊娠与念珠菌性外阴阴道炎，国外医学妇幼保健分。2003，14(6)343—345
7 Watson RW, O'Neill A, Brannigen AE, et al. Regulation of Fas antibody induced neutrophil apoptosis is both caspase and mitochondrial dependent.FEBS Lett. 1999;453:67-71.
8 TibbettsTA, Conneely OM, O'Malley BW. Progesterone via its receptor antagonizes the pro-inflammatory activity of estrogen in the mouse uterus. Biol Reprod.1999;60:1158-1165.
9 Yaffe K, Sawaya G, Lieberburg I,et al. Estrogen therapy in postmanopaul women:effects on cognitive function and dementia. JAMA, 1998, 279(9):688-695
10 White RF, Darkow DJ,Lang JL. Estrogen relaxes coronary arteries by opening BKCa channels through a cGMP-dependent mechanism. Circ Res,1995, 77:936-942
11 Tao J, Liu YQ, Li Y, Peng JL, Li L, Liu J, Shen X, Shen GX, Tu YT. Hypoxia: dual effect on the expression of transferrin receptor in human melanoma A375 cell line.Experimental dermatology 2007; 16:899-904.
12 D.A. Shear,R. Galani,S.W. Hoffman,D.G.Stein,progesterone protect agsinst necrotic damage and behaviroral abnomalities caused by traumatic brain injury,Exp.Neurol.l78(2002))59-67
13 Labombarda F,GonzaleZ SL,Gonzalez DM, Guennoun R,Schumacher M,de Nicola AF(2002) Cellular basis for progesterone neuroprotection in the injured spinal cord. J Neutrotrauma 19:343-355
14 Dai D,Wolf DM,Litman ES,et al.Progesterone inhibits human endometrial carcinoma cell growth and invasiveness:down-regulation of cellular adhesion molecules through progesterone B receptors.Cancer Res, 2002, 62(3): 881-886.
15 Nusbaum P, Laine C, Seveau S, Lesavre P, Halbwachs-Mecarelli L. Early membrane events in polymorphonuclear cell (PMN) apoptosis: membrane blebbing and vesicle release, CD43 and CD16 down-regulation and phosphatidylserine externalization. Biochemical Society transactions 2004; 32:477-479.
16 Davis BH, Olsen SH, Ahmad E, Bigelow NC. Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients. Archives of pathology &laboratory medicine 2006; 130:654-661.
17 Schroder AK, Uciechowski P, Fleischer D, Rink L. Crosslinking of CD66B on peripheral blood neutrophils mediates the release of interleukin-8 from intracellular storage. Human immunology 2006; 67:676-682.
18 Simons MP, Nauseef WM, Apicella MA. Interactions of Neisseria gonorrhoeae with adherent polymorphonuclear leukocytes. Infection and immunity 2005; 73:1971-1977.
19 Hasegawa T, Suzuki K, Sakamoto C, Ohta K, Nishiki S, Hino M, Tatsumi N, Kitagawa S. Expression of the inhibitor of apoptosis (LAP) family members in human neutrophils:up-regulation of cIAP2 by granulocyte colony-stimulating factor and overexpression of cIAP2 in chronic neutrophilic leukemia. Blood 2003; 101:1164-1171.
20 Cui X, Imaizumi T, Yoshida H, Tanji K, Matsumiya T, Satoh K. Lipopolysaccharide induces the expression of cellular inhibitor of apoptosis protein-2 in human macrophages. Biochimica et biophysica acta 2000; 1524:178-182.
21 Stehlik C, de Martin R, Binder BR, Lipp J. Cytokine induced expression of porcine inhibitor of apoptosis protein (iap) family member is regulated by NF-kappa B.Biochemical and biophysical research communications 1998; 243:827-832.
22 Chu ZL, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW. Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis C-IAP2 is under NF-kappaB control. Proceedings of the National Academy of Sciences of the United States of America 1997; 94:10057-10062.
23 Hawkins JV, Emmel EL, Feuer JJ, Nedelman MA, Harvey CJ, IGein HJ, Rozmiarek H,Kennedy AR, Lichtenstein GR, Billings PC. Protease activity in a hapten-induced model of ulcerative colitis in rats. Digestive diseases and sciences 1997;42:1969-1980.
1. Low N, Broutet N, Adu-Sarkodie Y, et al. Global control of sexually transmitted infections. Lancet, 2006, 368: 2001-2016.
2. Bozicevic I, Fenton KA, Martin IM, et al. Epidemiological correlates of asymptomatic gonorrhea. Sex Transm Dis, 2006, 33: 289-295.
3. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect, 1999, 75: 3-17.
4. Edwards JL, Apicella MA. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin Microbiol Rev,2004,17: 965-981, table of contents.
5. Rudel T, Scheurerpflug I, Meyer TF. Neisseria PilC protein identified as type-4 pilus tip-located adhesin. Nature, 1995, 373: 357-359.
6. Gulati S, Cox A, Lewis LA, et al. Enhanced factor H binding to sialylated Gonococci is restricted to the sialylated lacto-N-neotetraose lipooligosaccharide species: implications for serum resistance and evidence for a bifunctional lipooligosaccharide sialyltransferase in Gonococci. Infect Immun JT- Infection and immunity,2005,73(ll):7390-7.
7. Ram S, McQuillen DP, Gulati S, et al. Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. J Exp Med JT - The Journal of experimental medicine,1998,188(4):671-80.
8. Nowicki S, Ram P, Pham T, et al. Pelvic inflammatory disease isolates of Neisseria gonorrhoeae are distinguished by Clq-dependent virulence for newborn rats and by the sac-4 region. Infect Immun JT - Infection and immunity, 1997,65(6):2094-9.
9. Hamilton HL, Dillard JP.Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination. Mol Microbiol. 2006 Jan;59(2):376-85.
10. Harvey HA, Jennings MP, Campbell CA, et al. Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol Microbiol, 2001, 42: 659-672.
11. Kuhlewein C, Rechner C, Meyer TF, et al. Low - phosphate-dependent invasion resembles a general way for Neisseria gonorrhoeae to enter host cells. Infect Immun, 2006, 74: 4266-4273.
12. Pils S, Gerrard DT, Meyer A, et al. CEACAM3: an innate immune receptor directed against human-restricted bacterial pathogens. Int J Med Microbiol, 2008, 298:553-560.
13. Stocks, S. C, M. A. Kerr, C. Haslett, and I. Dransfield. 1995. CD66-de-pendent neutrophil activation: a possible mechanism for vascular selectin-mediated regulation of neutrophil adhesion. J. Leukoc. Biol. 58:40-48.
14. Schmitter, T., F. Agerer, L. Peterson, P. Munzner, and C. R. Hauck. 2004.Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific patho-gens. J. Exp. Med.199:35-46.
15. Timmerman MM, Shao JQ, Apicella MA. Ultrastructural analysis of the pathogenesis of Neisseria gonorrhoeae endometrial infection. Cell Microbiol, 2005, 7: 627-636.
16. Edwards JL, Apicella MA. Neisseria gonorrhoeae PLD directly interacts with Akt kinase upon infection of primary, human, cervical epithelial cells. Cell Microbiol,2006, 8: 1253-1271.
17. Marcinkiweicz J. Neutrophil chloramines: missing links between innate and acquired immunity[J]. Immunol Today, 1997,18: 577
18. S G Casey, W M Shafer, and J K Spitznagel. Neisseria gonorrhoeae survive intraleukocytic oxygen-independent antimicrobial capacities of anaerobic and aerobic granulocytes in the presence of pyocin lethal for extracellular gonococci. Infect Immun. 1986 May; 52(2): 384-389.
19. Quinn K, Henriques M, Parker T, et al. Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases. Am J Physiol Heart Circ Physiol,2008, 295: H1817-1824.
20. Bjerknes, R., H.-K. Guttormsen, C. O. Solberg, and L. M. Wetzler. 1995. Neisserial porins inhibit human neutrophil actin polymerization, degranu-lation, opsonin receptor expression, and phagocytosis but prime the neu-trophils to increase their oxidative burst. Infect. Immun. 63:160-167.
21. Lorenzen, D. R., D. Gunther, J. Pandit, T. Rudel, E. Brandt, and T. F. Meyer. 2000.Neisseria gonorrhoeae porin modifies the oxidative burst of human professional phagocytes. Infect. Immun. 68:6215-6222.
22. Lorenzen, D. R., D. Gunther, J. Pandit, T. Rudel, E. Brandt, and T. F.Meyer. 2000.Neisseria gonorrhoeae porin modifies the oxidative burst of human professional phagocytes. Infect. Immun. 68:6215-6222.
23. Hampton, M. B., A. J. Kettle, and C. C. Winterbourn. 1998. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92:3007-3017.
24. S R Johnson, B M Steiner, D D Cruce, G H Perkins, and R J Arko. Characterization of a catalase-deficient strain of Neisseria gonorrhoeae: evidence for the significance of catalase in the biology of N. gonorrhoeae. Infect Immun. 1993 April; 61(4):1232-1238.
25. Karen H. L. Lim,l Christopher E. Jones,l Rachel N. vanden Hoven,l Jennifer L.Edwards, Megan L. Falsetta, Michael A. Apicella, Michael P. Jennings, and Alastair G. McEwanl. Metal Binding Specificity of the MntABC Permease of Neisseria gonorrhoeae and Its Influence on Bacterial Growth and Interaction with Cervical Epithelial Cells. Infect Immun. 2008 August; 76(8): 3569-3576.
26. Kate L. Seib, Hsing-Ju Wu,Stephen P. Kidd, Michael A. Apicella, Michael P.Jennings,and Alastair G. McEwan. Defenses against Oxidative Stress in Neisseria gonorrhoeae: a System Tailored for a Challenging Environment. Microbiology and Molecular Biology Reviews, June 2006;70(2): 344-361
27. Susan Turner, Eleanor Reid, Harry Smith, and Jeffrey Cole. A novel cytochrome c peroxidase from Neisseria gonorrhoeae: a lipoprotein from a Gram-negative bacterium. Biochem J. 2003 August 1; 373(Pt 3): 865-873.
28. Seib, K. L., M. P. Jennings, and A. G McEwan. 2003. A Sco homologue plays a role in defense against oxidative stress in pathogenic Neisseria. FEBS Letters, Volume 546, Issue 2, Pages 411-415
29. Rest, R. F., J. Liu, R. Talukdar, J. V. Frangipane, and D. Simon. 1994. Interaction of pathogenic Neisseria with host defenses. What happens in vivo? Ann. N. Y. Acad. Sci.730:182-196.
30. ohannsen DB Johnston DM,Koymen HO , et al . A Neisseria gonorrhoeae immunoglobulin Al protease mutant is infectious in the human challenge model of urethral infection. [J]Infec Immun , 1999 ,67 (6):3009-3013.
31. Masri HP, Cornelissen CN. Specific Ligand Binding Attributable to Individual Epitopes of Gonococcal Transferrin Binding Protein A. [J ] . Infect Immun , 2002 ,70(2) :732-740
32. Lin L, Ayala P, Larson J, Mulks M, Fukuda M, Carlsson SR, Enns C, So M. The Neisseria type 2 IgAl protease cleaves LAMPl and promotes survival of bacteria within epithelial cells. Mol Microbiol. 1997 Jun;24(5):1083-94.
33. K(?) llstrom H , Islam MS , Berggren PO ,et al. Cell signaling by the type IV P I li of pathogenic neisseria. J Biol Chem, 1998 ,273(34):21777-21782.
34. Rudel T , Schmid A , Benz R , et al . Modulation of neisseria porin(PorB) by cytosolic ATP/ GTP of target cells : parallels between pathogen accommodation and mitochondrial endosymbiosis. Cell,1996,85(3): 391-402.
35. Ayala P , Vasquez B , Wetzler L ,et al . Neisseria gonorrhoeae porin P1.B induces endosome exocytosis and a redistribution of Iampl to the plasma membrane. Infection and Immunity ,2002 ,70 (11): 5965-5971.
36. Cauci S, Culhane JF. Modulation of vaginal immune response among pregnant women with bacterial vaginosis by Trichomonas vaginalis, Chlamydia trachomatis,Neisseria gonorrhoeae, and yeast. Am J Obstet Gynecol, 2007,196:133 el31-137.
37. van Ulsen P,Tommassen J. Protein secretion and secreted proteins in pathogenic Neisseriaceae. FEMS Microbiol Rev, 2006, 30: 292-319.
38. Derocco AJ, Yost-Daljev MK, Kenney CD, et al. Kinetic analysis of ligand interaction with the gonococcal transferrin-iron acquisition system. Biometals, 2008 Dec 2.
39. Biswas, G D : Anderson, J E : Sparling, P F. Cloning and functional characterization of Neisseria gonorrhoeae tonB, exbB and exbD genes. Mol-Microbiol. 1997 Apr;24(1): 169-79
40. Ronpirin C,Jerse AE,Cornelissen CN.Gonococcal Genes Encoding Transferrin-Binding Proteins A and B Are Arranged in a Bicistronic Operon but Are Subject to Differential Expression.[J]Infect Immun,2001,69(10):6336-6347.
41. Viscidi RP, Demma JC, Gu J, et al. Comparison of sequencing of the por gene and typing of the opa gene for discrimination of Neisseria gonorrhoeae strains from sexual contacts. J Clin Microbiol JT - Journal of clinical microbiology,2000,38(12):4430-8.
42. Jennifer M. Noto and Cynthia Nau Cornelissen. Identification of TbpA Residues Required for Transferrin-Iron Utilization by Neisseria gonorrhoeae. Infect Immun.2008 May; 76(5): 1960-1969.
43. Frangipane, J. V., and Rest, R. F. Anaerobic growth and cytidine 5'-monophospho-N-acetylneuraminic acid act synergistically to induce high-level serum resistance in Neisseria gonorrhoeae. (1993) Infect. Immun. 61,1657-1666.
44. G T Hoehn and V L Clark. Isolation and Nucleotide Sequence of the Gene (aniA)Encoding the Major Anaerobically Induced Outer Membrane Protein of Neisseria gonorrhoeae. Infect Immun. 1992 November; 60(11): 4695-4703.
45. Boulanger,M. J., andMurphy,M. E. P. Crystal structure of the soluble domain of the major anaerobically induced outer membrane protein (AniA) from pathogenic Neisseria: a new class of copper-containing nitrite reductases. (2002) J.Mol. Biol.315,1111-1127
46. Clark, V. L., Campbell, L. A., Palermo, D. A., Evans, T. M., and Klimpel,K.W.Induction and repression of outer membrane proteins by anaerobic growth of Neisseria gonorrhoeae. (1987) Infect. Immun. 55,1359-1364
47. Overton Tim W; Whitehead Rebekah; Li Ying; Snyder Lori A S; Saunders Nigel J;Smith Harry; Cole Jeff A. Coordinated Regulation of the Neisseria gonorrhoeae-truncated Denitrification Pathway by the Nitric Oxide-sensitive Repressor,NsrR, and Nitrite-insensitive NarQ-NarP. The Journal of biological chemistry 2006;281(44):33115-26.
48. Cardinale, J. A., and Clark, V. L. Expression of AniA, the Major Anaerobically Induced Outer Membrane Protein of Neisseria gonorrhoeae, Provides Protection against Killing by Normal Human Sera. (2000) Infect. Immun. 68, 4368-4369
49. Jean A. Cardinale and Virginia L. Clark. Determinants of nitric oxide steady-state levels during anaerobic respiration by Neisseria gonorrhoeae. Molecular Microbiology (2005) 58(1), 177-188
50. Potter AJ, Kidd SP, Edwards JL, et al. Thioredoxin reductase is essential for protection of Neisseria gonorrhoeae against killing by nitric oxide and for bacterial growth during interaction with cervical epithelial cells. J Infect Dis, 2009, 199:227-235.
51. Isabella V, Wright LF, Barth K, et al. cis- and trans-acting elements involved in regulation of norB (norZ), the gene encoding nitric oxide reductase in Neisseria gonorrhoeae. Microbiology, 2008,154: 226-239.
52. Ku SC, Schulz BL, Power PM, et al. The pilin O-glycosylation pathway of pathogenic Neisseria is a general system that glycosylates AniA, an outer membrane nitrite reductase. Biochem Biophys Res Commun, 2009, 378: 84-89.