title: Mathematical modelling reveals properties of TcdC required for it to be a negative regulator of toxin production in Clostridium difficile.
abstract: The role of the protein TcdC in pathogenicity of the bacterium Clostridium difficile is currently unclear: conflicting reports suggest it is either a negative regulator of toxin production or, on the other hand, has no effect on virulence at all. We exploit a theoretical approach by taking what is known about the network of proteins surrounding toxin production by C. difficile and translating this into a mathematical model. From there it is possible to investigate a range of possible interactions (using numerical and asymptotic analyses), identifying properties of TcdC which would make it a realistic candidate as a toxin inhibitor. Our findings imply that if TcdC is really an inhibitor of toxin production then TcdC production should be at least as fast as that of the protein TcdR and TcdC should remain in the cells throughout growth. These are experimentally-testable hypotheses and are equally applicable to alternative candidates for toxin production inhibition.
authors.affiliation: School of Mathematics and Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK, s.jabbari@bham.ac.uk.
authors.forename: Sara
authors.initials: S
authors.lastname: Jabbari
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Cartman
authors.forename: John R
authors.initials: JR
authors.lastname: King
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016360:Clostridioides difficile / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004768:Enterotoxins / Q000096:biosynthesis* / Q000235:genetics; D053263:Gene Regulatory Networks; D005798:Genes, Bacterial; D044404:Genomic Islands; D006801:Humans; D055641:Mathematical Concepts; D008954:Models, Biological; D017711:Nonlinear Dynamics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D012097:Repressor Proteins; C105615:TcdC protein, Clostridium difficile; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; C549683:toxin R, Clostridium difficile