THE ROLE OF BACTERIAL AMYLOID FIBRILS IN ESCHERICHIA COLI COMPLEMENT RESISTANCE

Abstract

Strains of Escherichia coli may exist as a beneficial human commensal or a pathogen capable of causing morbidity and mortality. Of the E. coli which causes human disease, many strains which cause bacteremia have been identified as possessing virulence factors which make them more resistant to the complement system. The bacterial amyloid fibril, curli, functions in bacterial adherence and the formation of biofilm. Curli-producing parental and curli-deficient mutant E. coli was compared in its survival to human complement, using in vitro serum sensitivity assays. Results showed an increase in the survival of curli-producing E. coli, which suggested that curli defends against complement killing. An in vivo murine model of E. coli-induced sepsis demonstrated that curli-producing bacteria also survived significantly better in the blood of mice. Immunostaining and flow cytometry was done to determine if parental and mutant strains of E. coli differentially bind to complement components C1q and C3. Results demonstrated that curli increases binding of C1q, but does not affect C3 binding. Blocking the classical pathway suggested that, in these assays, the classical pathway was the major contributor to complement activation and curli inhibits its activity. In addition, blocking the alternative pathway supported that the classical pathway was the main mechanism for complement activation and suggested that curli is not involved in protecting E. coli against alternative pathway activation. Results of this study conclude that curli defends E. coli against complement killing via inhibition of the classical complement pathway.