Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection.
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.
Ngampasutadol
Jutamas
J
Section of Infectious Diseases, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA.
Ram
Sanjay
S
Blom
Anna M
AM
Jarva
Hanna
H
Jerse
Ann E
AE
Lien
Egil
E
Goguen
Jon
J
Gulati
Sunita
S
Rice
Peter A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001770:Blood Bactericidal Activity / Q000276:immunology; D050716:Complement C4b-Binding Protein / Q000378:metabolism* / Q000502:physiology; D006069:Gonorrhea / Q000097:blood* / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D002679:Pan troglodytes / Q000097:blood / Q000276:immunology / Q000382:microbiology; D018272:Porins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity
D050716:Complement C4b-Binding Protein; D018272:Porins