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 normal protective gut flora and enables C. difficile to colonize the colon. C. difficile damage host tissu by secreting toxins and disseminates by forming spores. The toxins encoding genes, tcdA and tcdB are part of a pathogenicity locus, which also carry the gene tcdR that codes for the toxin genes positive regulator. TcdR is an alternate sigma factor that initiates transcription at tcdA an tcdB promoters. Alternate sigma factors are known to regulate virulence and virulence associated genes in many pathogenic bacteria. Mutation in tcdR affected both toxin production and sporulation in C. difficile. Transcriptome analyses revealed many differentially expressed sporulation genes in tcdR mutant.
First aim of this project will test the role of TcdR in C. difficle sporulation and the second aim will characterize mutations in tcdR upstream that are important for its transcription.
Aims of this study promises to provide critical information on gene regulatoy networks that are important for C. difficile pathogenesis. These findings will positively impact th pursuit of novel therapeutics to treat C. difficile infections.
Clostridium difficile infects thousands of hospitalized patients every year causing significant morbidity and mortality. C. difficile spores play a pivotal role in he transmission of the pathogen in the hospital environment. During infection, the spores eventually germinate, and the vegetative bacterial cells produce toxins that damage host tissue. In this project we propose to determine regulatory networks that link toxin production and sporulation in C. difficile.
| Girinathan, Brintha Parasumanna; Ou, Junjun; Dupuy, Bruno et al. (2018) Pleiotropic roles of Clostridium difficile sin locus. PLoS Pathog 14:e1006940 |
| Girinathan, Brintha P; Monot, Marc; Boyle, Daniel et al. (2017) Effect oftcdRMutation on Sporulation in the EpidemicClostridium difficileStrain R20291. mSphere 2: |
| Girinathan, Brintha Parasumanna; Braun, Sterling; Sirigireddy, Apoorva Reddy et al. (2016) Importance of Glutamate Dehydrogenase (GDH) in Clostridium difficile Colonization In Vivo. PLoS One 11:e0160107 |
