Abstract and Biography - Jimmy Ballard

Abstract

Suppressing Toxin Receptor Expression During C. difficile Infection

Clostridioides difficile is a leading cause of hospital-associated infection and occurs most commonly in patients undergoing antibiotic treatment.  C. difficile disease is mediated by bacterial toxins released into the colon.  The intracellular bacterial toxin, TcdB, is a major C. difficile virulence factor.  TcdB is indispensable to virulence and an important drug and vaccine target.  Research in the Ballard lab seeks to determine the mechanism through which TcdB is released from C. difficile and then how TcdB enters host cells.  In recent work, studies have focused on blocking expression of a key receptor (CSPG4) known to be important for TcdB’s ability to bind to target cells.  Using a combination of approaches, the Ballard research group has identified signaling networks important for CSPG4 expression.  Inhibitors targeting one of these signaling pathways were found to block CSPG4 transcription and eliminate this receptor from cells that would otherwise be targeted by TcdB.  Using a rodent model of C. difficile infection, experiments have shown that reducing CSPG4 expression in the mouse colon protects mice from severe disease.  Collectively, these studies and results support the idea of blocking TcdB receptor expression as a novel method of preventing C. difficile disease.

Bio-Summary

Dr. Jimmy Ballard is George Lynn Cross Professor and Chairman in the Department of Microbiology and Immunology at the University of Oklahoma Health Sciences Center.  Dr. Ballard is also the PI/Director of the Oklahoma Center for Microbial Pathogenesis and Immunity Phase I CoBRE.  Dr. Ballard’s research focuses on the biochemical functions of bacterial toxins and the role of these virulence factors in disease.  Dr. Ballard has studied toxins produced by gram positive bacteria for over 30 years, with an emphasis on anthrax toxin and toxins produced by pathogenic Clostridia.  Over the past decade his lab has defined key differences between C. difficile TcdB from hypervirulent and historical strains of this important human pathogen.  Dr. Ballard has authored ~90 manuscripts and is a Fellow in the American Academy of Microbiology.