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Protection from Lethal Clostridioides difficile Infection via Intraspecies
Competition for Cogerminant.

Authors	Leslie JL, Jenior ML, Vendrov KC, Standke AK, Barron MR, O'Brien TJ, Unverdorben L, Thaprawat P, Bergin IL, Schloss PD, Young VB
Submitted By	Submitted Externally on 12/3/2021
Status	Published
Journal	mBio
Year	2021
Date Published	3/1/2021
Volume : Pages	12 : Not Specified
PubMed Reference	33785619
Abstract	Clostridioides difficile, a Gram-positive, spore-forming bacterium, is the primary cause of infectious nosocomial diarrhea. Antibiotics are a major risk factor for C. difficile infection (CDI), as they disrupt the gut microbial community, enabling increased germination of spores and growth of vegetative C. difficile To date, the only single-species bacterial preparation that has demonstrated efficacy in reducing recurrent CDI in humans is nontoxigenic C. difficile Using multiple infection models, we determined that precolonization with a less virulent strain is sufficient to protect from challenge with a lethal strain of C. difficile, surprisingly even in the absence of adaptive immunity. Additionally, we showed that protection is dependent on high levels of colonization by the less virulent strain and that it is mediated by exclusion of the invading strain. Our results suggest that reduction of amino acids, specifically glycine following colonization by the first strain of C. difficile, is sufficient to decrease germination of the second strain, thereby limiting colonization by the lethal strain.IMPORTANCE Antibiotic-associated colitis is often caused by infection with the bacterium Clostridioides difficile In this study, we found that reduction of the amino acid glycine by precolonization with a less virulent strain of C. difficile is sufficient to decrease germination of a second strain. This finding demonstrates that the axis of competition for nutrients can include multiple life stages. This work is important, as it is the first to identify a possible mechanism through which precolonization with C. difficile, a current clinical therapy, provides protection from reinfection. Furthermore, our work suggests that targeting nutrients utilized by all life stages could be an improved strategy for bacterial therapeutics that aim to restore colonization resistance in the gut.

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