Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 59, Issue 12, Pages 7447-7457Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01357-15
Keywords
-
Categories
Funding
- ContraFect Corp.
- Bridges to Better Medicine Technology Innovation Fund
- Iris and Junming Le Foundation
- Rockefeller Center for Clinical and Translational Science (RUCCTS) from the National Center for Advancing Translational Sciences (NCATS, National Institutes of Health [NIH] Clinical and Translational Science Award [CTSA] program) [UL1 TR000043]
Ask authors/readers for more resources
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 a C. difficile strain, CD630, which we named PlyCD. PlyCD was found to have lytic activity against specific C. difficile strains. However, the recombinantly expressed catalytic domain of this protein, PlyCD(1-174), displayed significantly greater lytic activity (>4-log kill) and a broader lytic spectrum against C. difficile strains while still retaining a high degree of specificity toward C. difficile versus commensal clostridia and other bacterial species. Our data also indicated that noneffective doses of vancomycin and PlyCD(1-174) when combined in vitro could be significantly more bactericidal against C. difficile. In an ex vivo treatment model of mouse colon infection, we found that PlyCD(1-174) functioned in the presence of intestinal contents, significantly decreasing colonizing C. difficile compared to controls. Together, these data suggest that PlyCD(1-174) has potential as a novel therapeutic for clinical application against C. difficile infection, either alone or in combination with other preexisting treatments to improve their efficacy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available