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Infect Immun 2018 Jul 23;86(8):e00326-18

Cysteine desulfurase IscS2 plays a role in oxygen resistance in Clostridium difficile.

Giordano N, Hastie JL, Smith AD, Foss ED, Gutierrez-Munoz DF, Carlson PE Jr

Abstract

Clostridium difficile is an anaerobic, spore-forming bacterium capable of colonizing the gastrointestinal tract of humans following disruption of the normal microbiota, typically from antibiotic therapy for an unrelated infection. With approximately 500,000 confirmed infections leading to 29,000 deaths per year in the United States, C. difficile infection (CDI) is an urgent public health threat. We previously determined C. difficile survives in up to 3% oxygen. Low levels of oxygen are present in the intestinal tract with the higher concentrations being associated with the epithelial cell surface. Additionally, antibiotic treatment, the greatest risk factor for CDI, increases intestinal oxygen concentration. Therefore, we hypothesized that the C. difficile genome encodes mechanisms for survival during oxidative stress. Previous data have shown that cysteine desulfurases involved in iron-sulfur cluster assembly are involved in protecting bacteria from oxidative stress. In this study, deletion of a putative cysteine desulfurase (Cd630_12790/IscS2) involved in the iron sulfur cluster (Isc) system caused a severe growth defect in the presence of 2% oxygen. Additionally, this mutant delayed colonization in a conventional mouse model of CDI, and failed to colonize in a germ-free model, which has higher intestinal oxygen levels. These data imply an undefined role for this cysteine desulfurase in protecting C. difficile from low levels of oxygen in the gut.


Category: Journal Article
PubMed ID: #29866903 DOI: 10.1128/IAI.00326-18
PubMed Central ID: #PMC6056869
Includes FDA Authors from Scientific Area(s): Biologics Tobacco
Entry Created: 2018-01-28 Entry Last Modified: 2018-08-05
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