Spore-forming bacteria encompass a diverse range of genera and species, including important human and animal pathogens, and food contaminants. Clostridioides difficile is one such bacterium and is a global health threat because it is the leading cause of antibiotic-associated diarrhoea in hospitals. A crucial mediator of C. difficile disease initiation, dissemination and re-infection is the formation of spores that are resistant to current therapeutics, which do not target sporulation. Here, we show that cephamycin antibiotics inhibit C. difficile sporulation by targeting spore-specific penicillin-binding proteins. Using a mouse disease model, we show that combined treatment with the current standard-of-care antibiotic, vancomycin, and a cephamycin prevents disease recurrence. Cephamycins were found to have broad applicability as an anti-sporulation strategy, as they inhibited sporulation in other spore-forming pathogens, including the food contaminant Bacillus cereus. This study could directly and immediately affect treatment of C. difficile infection and advance drug development to control other important spore-forming bacteria that are problematic in the food industry (B. cereus), are potential bioterrorism agents (Bacillus anthracis) and cause other animal and human infections.
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The data that support the findings of this study are available from the corresponding author on reasonable request.
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This work was supported by the Australian National Health and Medical Research Council grant APP1145760 and the Australian Research Council Future Fellowship FT12010077 awarded to D.L.
The authors declare no competing interests.
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Srikhanta, Y.N., Hutton, M.L., Awad, M.M. et al. Cephamycins inhibit pathogen sporulation and effectively treat recurrent Clostridioides difficile infection. Nat Microbiol (2019) doi:10.1038/s41564-019-0519-1
Nature Reviews Gastroenterology & Hepatology (2019)