Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein

PLoS Pathog. 2008 Aug 29;4(8):e1000140. doi: 10.1371/journal.ppat.1000140.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism*
  • Antibodies, Bacterial / metabolism*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Complement Activation*
  • Complement C4b / genetics
  • Complement C4b / metabolism
  • Complement C4b-Binding Protein / genetics
  • Complement C4b-Binding Protein / metabolism*
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Gene Expression Regulation, Bacterial / genetics
  • Humans
  • Mutation
  • O Antigens / genetics
  • O Antigens / metabolism
  • Protein Binding / genetics
  • Yersinia Infections / genetics
  • Yersinia Infections / metabolism
  • Yersinia enterocolitica / genetics
  • Yersinia enterocolitica / metabolism*


  • Adhesins, Bacterial
  • Ail protein, Yersinia enterocolitica
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Complement C4b-Binding Protein
  • O Antigens
  • YadA protein, Yersinia
  • Complement C4b
  • Fibrinogen