title: The Regulatory Networks That Control Clostridium difficile Toxin Synthesis.
abstract: The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection.
authors.affiliation: Laboratoire Pathogenèse des Bactéries Anaérobes, Department of Microbiology, Institut Pasteur, 25 rue du Dr Roux Paris, Paris 75015, France. isabelle.martin-verstreate@pasteur.fr.|UFR Sciences du vivant, University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris 75015, France. isabelle.martin-verstreate@pasteur.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martin-Verstraete
authors.affiliation: Laboratoire Pathogenèse des Bactéries Anaérobes, Department of Microbiology, Institut Pasteur, 25 rue du Dr Roux Paris, Paris 75015, France. johann.peltier@pasteur.fr.
authors.forename: Johann
authors.initials: J
authors.lastname: Peltier
authors.affiliation: Laboratoire Pathogenèse des Bactéries Anaérobes, Department of Microbiology, Institut Pasteur, 25 rue du Dr Roux Paris, Paris 75015, France. bdupuy@pasteur.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dupuy
mesh_terms: D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics; D057465:Catabolite Repression; D016360:Clostridioides difficile / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; D014157:Transcription Factors; D011392:Proline; D003545:Cysteine
keywords: C. difficile; PaLoc; c-di-GMP; carbon catabolite repression system; growth phase; quorum sensing; sporulation; stress signals; toxin regulation