Molecular Details of Serum Resistance of Yersinia enterocolitica

In complement activation, Factor H (FH) and C4b-binding protein (C4bp) are the key regulators that prevent the complement cascade from attacking host tissues. Some bacteria may bind and deposit these regulators on their own surfaces and thus provide themselves with an efficient means to avoid complement activation. In consequence, bacteria resist complement-mediated lysis and opsonin-dependent phagocytosis. This study has demonstrated that Y. enterocolitica, similar to many other pathogens, recruits both FH and C4bp to its surface to ensure protection against the complement-mediated killing. YadA and Ail, the most crucial serum resistance factors of Y.enterocolitica, mediate the binding of FH and C4bp. FH - YadA interaction involves multiple higher structural motifs on the YadA stalk and the short consensus repeats (SCRs) of the entire polypeptide chain of FH. The Ail binding site on FH has been located to SCRs 6 and 7. The binding site for FH on Ail, however, remains undetermined. Both YadA- and Ail-bound regulators display full cofactor activity for FI-mediated cleavage of C3b/C4b. FH/C4bp-binding characteristics do, however, differ between YadA and Ail. In addition, Ail captures the regulators only in the absence of blocking lipopolysaccharide O-antigen and outer core, whereas YadA binds FH/C4bp independent of the presence of other surface factors Independent of mode of binding, however, YadA and Ail provide Y. enterocolitica a means to avoid complement-mediated lysis, enhancing chances for the bacteria to survive in the host during various phases of infection.

Human beings provide a home for a myriad of microbes. Many microbes produce vitamins and nutrients, ferment food, break down toxic chemicals, and protect us from pathogenic microbes which we encounter every day. The latter, however, often find ways to cause infection, exploiting a wide range of strategies to penetrate physical barriers such as skin or mucous membranes and to survive and persist in the host. The first obstacle they must combat is the action of the non-specific innate immune system. One of its essential arms is the complement system, the first line of defense activated immediately upon pathogen entry. The importance of the complement system in host defense against invading pathogens is reflected by increased susceptibility to microbial infection of individuals deficient in certain complement components. Complement is bactericidal against Gram-negative bacteria, it acts as an opsonin, and its cleavage products contribute to induction of inflammation. That pathogens adapt quickly to environmental changes makes them tenacious opponents. They express surface factors to manipulate the host complement system and avoid complement-mediated recognition and eradication. This study has demonstrated that an enteropathogic bacterium Y. enterocolitica binds host complement regulators to avoid complement-mediated lysis, enhancing chances for the bacteria to survive in the host during various phases of infection.