Impacts of on oxygen sensitivity, gene expression, and murine infection in 630∆.

J Bacteriol

Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

Published: January 2025

infection (CDI), characterized by colitis and diarrhea, afflicts approximately half a million people in the USA every year, burdening both individuals and the healthcare system. 630Δ is an erythromycin-sensitive variant of the clinical isolate 630 and is commonly used in the research community due to its genetic tractability. 630Δ possesses a point mutation in , an autoregulated transcriptional repressor that regulates oxidative stress resistance genes. This point mutation results in a constitutively de-repressed PerR operon in 630Δ. To address the impacts of on phenotypes relevant for oxygen tolerance and relevant to a murine model of CDI, we corrected the point mutant to restore PerR function in 630∆ (herein, 630∆). We demonstrate that there is no difference in growth between 630Δ and 630Δ under anaerobic conditions or when exposed to concentrations of O that mimic those found near the surface of the colonic epithelium. However, 630∆ is more sensitive to ambient oxygen than 630∆, which coincides with alterations in expression of a variety of -dependent and -independent genes. Finally, we show that 630∆ and 630∆ do not differ in their ability to infect and cause disease in a well-established murine model of CDI. Together, these data support the hypothesis that the mutation in 630∆ arose as a result of exposure to ambient oxygen and that the mutation in 630∆ is unlikely to impact CDI-relevant phenotypes in laboratory studies.IMPORTANCE is a diarrheal pathogen and a major public health concern. To improve humans' understanding of , a variety of isolates are used in research, including 630Δ. 630Δ is a derivative of the clinical isolate 630 and is commonly studied because it is genetically manipulable. Previous work showed that a mutation in in 630Δ results in a dysregulated oxidative stress response, but no work has been done to characterize -dependent effects on the transcriptome or to determine impacts of during infection. Here, we identify transcriptomic differences between 630∆ 630∆ exposed to ambient oxygen and demonstrate that there is no strain-based difference in burdens in murine infection.

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http://dx.doi.org/10.1128/jb.00468-24DOI Listing

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