Deciphering strain differences in CodY regulation of Clostridioides difficile sporulation Open Access
Monteiro, Marcos (Summer 2025)
Abstract
Clostridioides difficile is an anaerobic and spore-forming pathogen that causes severe diarrhea, colitis, and even death. C. difficile infections are considered a burden to the healthcare and the economic systems of the U.S. Since spores are the only mode of transmission, the formation of spores is crucial for the spread of C. difficile. When a host ingests spores, the spores travel through the gastrointestinal tract, reaching the intestines where the spores sense bile salts. By sensing bile salts, spores are triggered to become vegetative cells. Vegetative cells continue traveling the gastrointestinal tract, reaching the colon. In the colon, C. difficile can colonize it. In this environment, nutrient availability is limited, prompting intracellular responses to adapt to the conditions. In C. difficile, nutrient availability is sensed by various nutritional regulators, including CodY. CodY is a global transcriptional regulator that senses branched-chain amino acids (BCAA) and guanosine-triphosphate (GTP). In rich growth conditions, BCAA and GTP bind to CodY, causing conformational changes that increase its affinity to bind specific sequences of DNA. When there are low concentrations of BCAA and GTP, BCCA and GTP are not bound to CodY, and the affinity of CodY to DNA decreases. In C. difficile, CodY is known to repress toxin production and sporulation. However, the direct CodY-regulated factors that control sporulation are not well understood. In this work, we confirm and expand the knowledge that CodY represses the initiation of sporulation in two different strains of C. difficile and that CodY continues to have a role in the regulation of sporulation at the stationary phase. Additionally, we identified several direct CodY-regulated factors in both the 630∆erm and UK1 strains that are differentially regulated between the strains and unique in one of the strains. We further determined the effect of many direct CodY-regulated factors on sporulation in strain UK1 and the UK1 codY mutant. This work illustrates that CodY has a greater impact on the transcriptome of UK1 and that many factors under CodY regulation impact sporulation in C. difficile.
Table of Contents
Abstract
Acknowledgments
Table of Contents
List of Tables and Figures
Chapter 1: Introduction…………………………………………………………………………………..1
Chapter 2: Deciphering strain differences in CodY regulation of Clostridioides difficile sporulation…………………………………………………………………………………………….…28
Chapter 3: Discussion…………………………………………………………………………………..72
About this Dissertation
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Primary PDF
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Deciphering strain differences in CodY regulation of Clostridioides difficile sporulation () | 2025-07-29 01:13:56 -0400 |
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Supplemental Files
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RNA-Seq analysis of 630∆erm codY compared to 630∆erm (RNA-Seq analysis) | 2025-07-06 18:12:18 -0400 |
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RNA-Seq analysis of UK1 codY compared to UK1 (RNA-Seq analysis) | 2025-07-06 18:12:27 -0400 |
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Differentially direct CodY-regulated factors in 630∆erm and UK1 (Compiled table of CodY-regulated factors ) | 2025-07-06 18:12:39 -0400 |
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