Neisseria gonorrhoeae is the causative agent of
gonorrhea, a disease that is restricted to humans.
Complement forms a key arm of the innate immune system that combats gonococcal
infections. N. gonorrhoeae uses its outer membrane
porin (Por) molecules to bind the classical pathway of
complement down-regulatory
protein C4b-binding protein (C4bp) to evade killing by human
complement. Strains of N. gonorrhoeae that resisted killing by human serum
complement were killed by serum from rodent, lagomorph, and primate species, which cannot be readily infected experimentally with this organism and whose C4bp molecules did not bind to N. gonorrhoeae. In contrast, we found that Yersinia pestis, an organism that can infect virtually all mammals, bound species-specific C4bp and uniformly resisted serum
complement-mediated killing by these species. Serum resistance of gonococci was restored in these sera by human C4bp. An exception was serotype Por1B-bearing gonococcal strains that previously had been used successfully in a chimpanzee model of
gonorrhea that simulates human disease. Por1B gonococci bound chimpanzee C4bp and resisted killing by chimpanzee serum, providing insight into the host restriction of
gonorrhea and addressing why Por1B strains, but not Por1A strains, have been successful in experimental chimpanzee
infection. Our findings may lead to the development of better animal models for
gonorrhea and may also have implications in the choice of
complement sources to evaluate neisserial
vaccine candidates.