Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 44, Issue 1, Pages 69-73Publisher
ELSEVIER
DOI: 10.1016/j.ijantimicag.2014.03.007
Keywords
Clostridium difficile; High-throughput screen; Antibiotic discovery; Small-molecule library
Funding
- National Institutes of Health [NIH U54 A1 057168, NIH R01 AI068942]
- Global Alliance for TB Drug Development
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Clostridium difficile, a highly drug-resistant Gram-positive, spore-forming bacterium, remains a leading cause of hospital-acquired diarrhoea and antibiotic-associated colitis. Clinically, only a handful of antibiotics are used for treating C. difficile infection (CDI), suggesting a necessity for the development of new treatment options. Here we performed a high-throughput screen of 2000 drug-like compounds for inhibition of C. difficile. From this screen, one compound, 5-nitro-1,10-phenanthroline (5-NP), showed potent bactericidal effects in vitro. In addition, this compound displayed high potency towards other Clostridium spp. as well as Mycobacterium bovis but not towards other tested Gram-positive and Gram-negative bacteria. Furthermore, we show that this inhibition may proceed through a metal chelation-dependent mechanism. More importantly, preliminary evidence suggests moderate efficacy for this compound in treating CDI in a murine infection model. These results present a possible basis for the further development of this compound as an antibiotic treatment for CDI. (C) 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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