Nowicki S, Ram P, Pham T, Goluszko P, Morse S, Anderson G D, Nowicki B
Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, 77555-1062, USA.
Infect Immun. 1997 Jun;65(6):2094-9. doi: 10.1128/iai.65.6.2094-2099.1997.
The virulence mechanism of Neisseria gonorrhoeae in pelvic inflammatory disease (PID) is not well understood, and an objective diagnostic method to identify patients with PID is lacking. We investigated the hypothesis that development of PID was associated with a C1q-dependent virulence property of gonococcal strains. Recent development of a C1q-dependent experimental model of gonococcal infection (S. Nowicki, M. Martens, and B. Nowicki, Infect. Immun. 63:4790-4794, 1995) created an opportunity to evaluate this hypothesis in vivo. Therefore, the virulence of 32 clinical isolates (18 PID isolates and 14 local infection [LI] isolates) was evaluated in experimental rat pups. A serum bactericidal assay was used to characterize a gonococcal serum-resistant (ser(r)) phenotype. PCR primers designed to amplify a suitable-size gonococcal sac-4 DNA fragment (unique for serum-resistant donor JC1) were used to evaluate the association of serum-resistant genotype sac-4 with two phenotypes: C1q-dependent virulence expressed in vivo and resistance to bactericidal activity of human serum expressed in vitro. Strains were also characterized by auxotyping and serotyping. Of 32 gonococcal strains, 15 (46.7%) caused C1q-dependent bacteremia in rat pups and were sac-4 positive and ser(r). However, of the 15 isolates, 13 (87%) represented strains associated with human PID and 2 (13%) were associated with LI. None of the strains that were completely serum-sensitive (ser(s)) and sac-4 negative produced C1q-dependent bacteremia in rat pups, suggesting that both ser(r) and sac-4 were required for infection. The serum-resistant recombinant recipient of sac-4 produced C1q-dependent bacteremia in the rat model similarly to the serum-resistant donor of sac-4; the serum-sensitive parent strain did not produce bacteremia. These data suggest that sac-4-mediated serum resistance conferred C1q-dependent virulence and is a unique characteristic associated with PID. These newly identified features may contribute to the understanding of the pathogenic mechanism of PID-associated strains and open perspectives for establishing novel diagnostic methods.
淋病奈瑟菌在盆腔炎（PID）中的致病机制尚未完全明确，且缺乏用于识别PID患者的客观诊断方法。我们研究了PID的发生与淋球菌菌株的C1q依赖性致病特性相关这一假说。淋球菌感染的C1q依赖性实验模型的最新进展（S. Nowicki、M. Martens和B. Nowicki，《感染与免疫》63:4790 - 4794，1995年）为在体内评估该假说创造了机会。因此，我们在实验性幼鼠中评估了32株临床分离株（18株PID分离株和14株局部感染[LI]分离株）的毒力。采用血清杀菌试验来表征淋球菌血清抗性（ser(r)）表型。设计用于扩增合适大小的淋球菌sac - 4 DNA片段（血清抗性供体JC1所特有）的PCR引物，用于评估血清抗性基因型sac - 4与两种表型的关联：在体内表达的C1q依赖性毒力和在体外表达的对人血清杀菌活性的抗性。菌株还通过辅助分型和血清分型进行表征。在32株淋球菌菌株中，15株（46.7%）在幼鼠中引起了C1q依赖性菌血症，且为sac - 4阳性和ser(r)。然而，在这15株分离株中，13株（87%）代表与人类PID相关的菌株，2株（13%）与LI相关。所有完全血清敏感（ser(s)）且sac - 4阴性的菌株在幼鼠中均未产生C1q依赖性菌血症，这表明感染需要ser(r)和sac - 4。sac - 4的血清抗性重组受体在大鼠模型中产生的C1q依赖性菌血症与sac - 4的血清抗性供体相似；血清敏感的亲本菌株未产生菌血症。这些数据表明，sac - 4介导的血清抗性赋予了C1q依赖性毒力，是与PID相关的独特特征。这些新发现的特征可能有助于理解PID相关菌株的致病机制，并为建立新的诊断方法开辟前景。
