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© Bruno Dupuy, Claire Morvan, Institut Pasteur
Cellules végétative et spores de Clostridioides difficile / Vegative cells and spores of Clostridioides difficile
Publication : msphere

Effect of tcdR Mutation on Sporulation in the Epidemic Clostridium difficile Strain R20291

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in msphere - 15 Feb 2017

Brintha P. Girinathan, Marc Monot, Daniel Boyle, Kathleen N. McAllister, Joseph A. Sorg, Bruno Dupuy, Revathi Govind

Effect of tcdR Mutation on Sporulation in the Epidemic Clostridium difficile Strain R20291 Brintha P. Girinathan, Marc Monot, Daniel Boyle, Kathleen N. McAllister, Joseph A. Sorg, Bruno Dupuy, Revathi Govind mSphere Feb 2017, 2 (1) e00383-16; DOI: 10.1128/mSphere.00383-16

Clostridium difficile is an important nosocomial pathogen and the leading cause of hospital-acquired diarrhea. Antibiotic use is the primary risk factor for the development of C. difficile-associated disease because it disrupts normally protective gut flora and enables C. difficile to colonize the colon. C. difficile damages host tissue by secreting toxins and disseminates by forming spores. The toxin-encoding genes, tcdA and tcdB, are part of a pathogenicity locus, which also includes the tcdR gene that codes for TcdR, an alternate sigma factor that initiates transcription of tcdA and tcdB genes. We created a tcdR mutant in epidemic-type C. difficilestrain R20291 in an attempt to identify the global role of tcdR. A site-directed mutation in tcdRaffected both toxin production and sporulation in C. difficile R20291. Spores of the tcdR mutant were more heat sensitive than the wild type (WT). Nearly 3-fold more taurocholate was needed to germinate spores from the tcdR mutant than to germinate the spores prepared from the WT strain. Transmission electron microscopic analysis of the spores also revealed a weakly assembled exosporium on the tcdR mutant spores. Accordingly, comparative transcriptome analysis showed many differentially expressed sporulation genes in the tcdR mutant compared to the WT strain. These data suggest that regulatory networks of toxin production and sporulation in C. difficile strain R20291 are linked with each other.

http://msphere.asm.org/content/2/1/e00383-16