Using a Novel Lysin To Help Control Clostridium difficile Infections

As a consequence of excessive antibiotic therapies in hospitalized patients,Clostridium difficile , a Gram-positive anaerobic spore-forming intestinal pathogen, is the leading cause of hospital-acquired diarrhea and colitis. Drug treatments for these diseases are often complicated by antibiotic-resistant strains and a high frequency of treatment failures and relapse; therefore, novel nonantibiotic approaches may prove to be more effective. In this study, we recombinantly expressed a prophage lysin identified from aC. difficile strain, CD630, which we named PlyCD. PlyCD was found to have lytic activity against specificC. difficile strains. However, the recombinantly expressed catalytic domain of this protein, PlyCD1–174 , displayed significantly greater lytic activity (>4-log kill) and a broader lytic spectrum againstC. difficile strains while still retaining a high degree of specificity towardC. difficile versus commensal clostridia and other bacterial species. Our data also indicated that noneffective doses of vancomycin and PlyCD1–174 when combinedin vitro could be significantly more bactericidal againstC. difficile . In anex vivo treatment model of mouse colon infection, we found that PlyCD1–174 functioned in the presence of intestinal contents, significantly decreasing colonizingC. difficile compared to controls. Together, these data suggest that PlyCD1–174 has potential as a novel therapeutic for clinical application againstC. difficile infection, either alone or in combination with other preexisting treatments to improve their efficacy.