<2> CdtR Regulates TcdA and TcdB Production in Clostridium difficile
CdtR Regulates TcdA and TcdB Production in Clostridium difficile
Shelley A. Lyon, Melanie L. Hutton, Julian I. Rood, Jackie K. Cheung , Dena Lyras*
PLOS Pathogens DOI:10.1371/journal.ppat.1005758 July 14, 2016
Speaker: Kuang-Yu Chen (陳冠宇) Time: 14:00~15:00, Sep21, 2016
Commentator: Dr. Jenn-Wei Chen (陳振暐 老師) Place: Room 601
Abstract:
Clostridium difficile is a gram positive spore forming bacterium. Clostridium difficile-associate disease (CDAD) is a serious nosocomial infection. Infection with C. difficile can lead to pseudomembranous colitis and antibiotic-associated diarrhea. There are three toxins in C. difficile, TcdA, TcdB and binary toxin. Genes encoding for TcdA and TcdB belong to a pathogenic loci (PaLoc), while the gene coding for binary toxin belong to the Cdt loci. TcdA and TcdB act as monoglucosyltransferases that inactivates Rho GTPases, causing disruption of cell-cell junctions, which enhances epithelial permeability[1]. CDT, an ADP-ribosyltransferase, is not essential for disease but may be important for colonization during an infection, is regulated by CdtR[2]. In this study, the authors wanted to know the molecular relationship between these three toxin genes in the hypervirulentribotype 027 strains. Previous studies indicate that CdtR is a regulator of the CDT loci. Here, the authors find that CdtR can regulate not only CDT but also TcdA and TcdB production. Inactivation of cdtR decreased the level of HT29 and Vero cell toxicity by TcdA and TcdB. In a murine model, infection with cdtR mutant strains of C. difficile increased mice survival rate, and histopathology score were similar uninfected animals. In summary, CdtR is shown to be a global regulator of all three toxins in C. difficile. Future works will determine whether this phenomenon holds true for diverse strains of C. difficile.
References:
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2. Carter GP, Lyras D, Allen DL, Mackin KE, Howarth PM, O'Connor JR, et al. Binary toxin production in Clostridium difficile is regulated by CdtR, a LytTR family response regulator. J Bacteriol. 2007;189(20):7290-301. doi: 10.1128/JB.00731-07. PubMed PMID: 17693517; PubMed Central PMCID: PMCPMC2168464.