Deciphering strain differences in codY regulation of s sporulation.

Microbiology spectrum
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Keywords
Abstract

is an anaerobic, spore-forming pathogen that causes diarrhea, colitis, and even death. grows and replicates in the intestine as a vegetative bacillus, but must transition into a dormant spore to survive and transmit in the environment. The transformation into a spore is a complex developmental process that is regulated in response to conditions within the host, most notably nutrient limitation. Nutrient availability is sensed by through transcriptional regulators, such as CodY. CodY is a global nutritional gene regulator that controls gene expression in response to branched-chain amino acids (BCAAs) and guanosine-triphosphate (GTP). It was previously observed that CodY represses sporulation, but the impact of CodY on sporulation has differed considerably by strain. Here, we investigated the effects of CodY on gene expression during sporulation in the two common research strains 630 (ribotype 012) and UK1 (ribotype 027). We confirmed that CodY suppressed premature spore formation in both strains through time-elapsed sporulation assays with mutants. Through transcriptional analyses of mutant sporulation, we defined the similarities and differences in the CodY-dependent gene expression between strains. We also identified differences in putative CodY sites within the 630 and UK1 genomes that may influence CodY regulation. Finally, we performed CRISPRi knockdowns to examine the effects of selected CodY-regulated genes, demonstrating the impact of multiple CodY-dependent factors on sporulation.IMPORTANCE spore formation is crucial for transmission and survival of the bacterium. Spore formation is triggered by the availability of crucial nutrients, which CodY and other regulators sense. However, the mechanism by which CodY represses sporulation in is poorly understood. In this study, we identified several CodY-regulated factors that could play a role in sporulation both in 630 and UK1 strains. Our results show that many factors under the regulation of CodY can impact sporulation.

Year of Publication
2025
Journal
Microbiology spectrum
Pages
e0170625
Date Published
11/2025
ISSN
2165-0497
DOI
10.1128/spectrum.01706-25
PubMed ID
41247048
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