Binding of complement factor H to loop 5 of porin protein 1A:: A molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae

被引:223
作者
Ram, S [1 ]
McQuillen, DP
Gulati, S
Elkins, C
Pangburn, MK
Rice, PA
机构
[1] Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA
[2] Boston Med Ctr, Evans Mem Dept Clin Res, Boston, MA 02118 USA
[3] Boston Med Ctr, Dept Med, Boston, MA 02118 USA
[4] Univ N Carolina, Chapel Hill, NC 27599 USA
[5] Univ Texas, Ctr Hlth Sci, Tyler, TX 75708 USA
关键词
Neisseria gonorrhoeae; factor H; porin; serum resistance;
D O I
10.1084/jem.188.4.671
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Neisseria gonorrhoeae isolated from patients with disseminated infection are often of the porin (Por1A) serotype and resist killing by nonimmune normal human serum. The molecular basis of this resistance (termed stable serum resistance) in these strains has not been fully defined but is not related to sialylation of lipooligosaccharide Here we demonstrate that Por1A bearing gonococcal st rains bind more factor H, a critical downregulator of the alternative complement pathway, than their Por1B counterparts. This results in a sevenfold reduction in C3b, which is >75% converted to iC3b. Factor H binding to isogenic gonococcal strains that differed only in their porin serotype, confirmed that Por1A was the acceptor molecule for factor H. We identified a surface exposed re,region on the Por1A molecule that served as the binding site for factor H. We used gonococcal strains with hybrid Por1A/B molecules that differed in their surface exposed domains to localize the factor H binding site to loop 5 of`Por1A. This was confirmed by inhibition of factor H binding using synthetic peptides corresponding to the putative exposed regions of the porin loops. The addition of Por1A loop 5 peptide in a serum bactericidal assay, which inhibited binding of factor H to the bacterial surface, permitted 50% killing of an otherwise completely serum resistant gonococcal strain. Collectively, these data provide a molecular basis to explain serum resistance of Por1A strains of N. gonorrhocae.
引用
收藏
页码:671 / 680
页数:10
相关论文
共 60 条