Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Nat Microbiol. 2019 Dec;4(12):2237-2245. doi: 10.1038/s41564-019-0519-1. Epub 2019 Aug 12.
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.
产芽孢细菌包含了多种属和种，包括重要的人类和动物病原体以及食源性病原体。艰难梭菌就是这样一种细菌，它是一种全球健康威胁，因为它是医院中抗生素相关性腹泻的主要原因。艰难梭菌疾病起始、传播和再感染的一个关键介质是形成对当前治疗方法具有抗性的孢子，而这些治疗方法并不针对孢子形成。在这里，我们表明头孢菌素类抗生素通过靶向孢子特异性青霉素结合蛋白来抑制艰难梭菌的孢子形成。使用小鼠疾病模型，我们表明联合使用当前的标准护理抗生素万古霉素和头孢菌素可以预防疾病复发。头孢菌素类抗生素作为一种抗孢子形成策略具有广泛的适用性，因为它们抑制了包括食源性病原体蜡样芽孢杆菌在内的其他产芽孢病原体的孢子形成。这项研究可以直接影响艰难梭菌感染的治疗，并推进药物开发以控制食品工业中存在的其他重要产芽孢细菌（蜡样芽孢杆菌）、可能的生物恐怖主义剂（炭疽芽孢杆菌）以及引起其他动物和人类感染的细菌。
