Hypervirulent, multi-antibiotic resistant ribotypes of Clostridium difficile have emerged in the last decade and represent a severe threat to global health. As a Gram-positive, anaerobic, spore-forming pathogen C. difficile presents numerous challenges to therapeutic eradication. Currently, C. difficile infection (CDI) is both caused by and clinically managed with traditional antibiotics that indiscriminately eradicate pathogenic and commensal bacteria. These traditional antibiotics disrupt essential enzymes and/or pathways in bacteria and thus are unselective in their mechanism of action. This is problematic, as microflora represent one of the most successful defenses against CDI. To combat the detrimental effects of broad-spectrum agents on microflora, new approaches that eliminate the virulence of pathogens, but allow beneficial microbes to persist are promising avenues for new age antibacterial drug discovery. As a key regulator of virulence and antibiotic resistance in pathogenic microbes, we hypothesize that caseinolytic protease P (ClpP) represents a promising anti-virulence target for CDI. Indeed, previous research demonstrates that disruption of ClpP activity in pathogenic bacteria leads to attenuated virulence. To date, however, the structure and function of the ClpP system have not been defined in C. difficile. Our studies towards determining the biological significance and therapeutic potential of the ClpP system in C. difficile will be presented.

Behavior and biological significance of caseinolytic protease P in Clostridium difficile

255th National Meeting (2018)

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