Impacts of on Oxygen Sensitivity, Gene Expression, and Murine Infection in 630Δ

infection (CDI), characterized by colitis and diarrhea, afflicts approximately half a million people in the United States 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 630Δ (herein, 630Δ ). We demonstrate that there is no difference in growth between 630Δ and a 630Δ under anaerobic conditions or when exposed to concentrations of O that mimic those found near the surface of the colonic epithelium. However, 630Δ is more sensitive to ambient oxygen than 630Δ, which coincides with alterations in expression of a variety of -dependent and -independent genes. Finally, we show that 630Δ and 630Δ 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 630Δ arose as a result of exposure to ambient oxygen and that the mutation in 630Δ is unlikely to impact CDI-relevant phenotypes in laboratory studies.