Abstract
Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS) O-antigen (O-ag) and outer core (OC) do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp), an inhibitor of both the classical and lectin pathways of complement. To identify the C4bp receptors on Y. enterocolitica serotype O:3 surface, a set of mutants expressing YadA, Ail, O-ag, and OC in different combinations was tested for the ability to bind C4bp. The studies showed that both YadA and Ail acted as C4bp receptors. Ail-mediated C4bp binding, however, was blocked by the O-ag and OC, and could be observed only with mutants lacking these LPS structures. C4bp bound to Y. enterocolitica was functionally active and participated in the factor I-mediated degradation of C4b. These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host.
Highlights
Yersinia enterocolitica is a food-borne enteric pathogen of humans and animals
Similar to other pathogens Y. enterocolitica binds the alternative pathway (AP) inhibitor factor H (FH) [40] and we recently demonstrated that Y. enterocolitica serotype O:3 bacteria use both YadA and Ail to bind the AP regulator FH (Biedzka-Sarek et al, submitted for publication) but no studies on possible regulation of the CP or C4b-binding protein (C4bp) binding to the bacterium have been reported
In order to study whether Y. enterocolitica binds the classical and lectin pathway complement inhibitor C4bp serotype O:3, O:8, O:9 and biotype 1A strains were incubated with 125I-C4bp and phase-separated from unbound 125I-C4bp by centrifugation through 20% sucrose
Summary
Yersinia enterocolitica is a food-borne enteric pathogen of humans and animals. The invasive strains predominantly belong to serotypes O:3, O:9, O:5,27 and O:8. Successful colonization of the intestinal tract is the prerequisite for Y. enterocolitica infection. Bacteria pass through the acidic content of the stomach and reach the small intestine. Soon after invading the M cells, bacteria enter the lamina propria and encounter innate and adaptive immune responses [1]. Y. enterocolitica can cause enterocolitis, mesenteric lymphadenitis and, as a post-infectious complication, reactive arthritis [2]. Mechanisms whereby Y. enterocolitica can evade the immune system killing and why it causes reactive arthritis are not fully understood
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