University of Virginia Patent Foundation

Carrie Adeline Cowardin

William A Petri

is the most common hospital acquired pathogen in the United States, and infection is in many cases fatal. Toxins A and B are its major virulence factors, but increasingly a third toxin may be present, known astransferase (CDT). An ADP-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. It is disclosed herein that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a novel Toll-like Receptor 2 (TLR2) dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, it is disclosed that restoration of TLR2 deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressingand demonstrate a mechanism by which this binary toxin subverts the host immune response.

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St. Louis, MO, United States of America

Carrie Adeline Cowardin