title: SecB-like chaperone controls a toxin-antitoxin stress-responsive system in Mycobacterium tuberculosis.
abstract: A major step in the biogenesis of newly synthesized precursor proteins in bacteria is their targeting to the Sec translocon at the inner membrane. In gram-negative bacteria, the chaperone SecB binds nonnative forms of precursors and specifically transfers them to the SecA motor component of the translocase, thus facilitating their export. The major human pathogen Mycobacterium tuberculosis is an unusual gram-positive bacterium with a well-defined outer membrane and outer membrane proteins. Assistance to precursor proteins by chaperones in this bacterium remains largely unexplored. Here we show that the product of the previously uncharacterized Rv1957 gene of M. tuberculosis can substitute for SecB functions in Escherichia coli and prevent preprotein aggregation in vitro. Interestingly, in M. tuberculosis, Rv1957 is clustered with a functional stress-responsive higB-higA toxin-antitoxin (TA) locus of unknown function. Further in vivo experiments in E. coli and in Mycobacterium marinum strains that do not possess the TA-chaperone locus show that the severe toxicity of the toxin was entirely inhibited when the antitoxin and the chaperone were jointly expressed. We found that Rv1957 acts directly on the antitoxin by preventing its aggregation and protecting it from degradation. Taken together, our results show that the SecB-like chaperone Rv1957 specifically controls a stress-responsive TA system relevant for M. tuberculosis adaptive response.
authors.affiliation: Laboratoire de Microbiologie et Génétique Moléculaire, Centre National de la Recherche Scientifique and Université Paul Sabatier, F-31000 Toulouse, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bordes
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cirinesi
authors.forename: Roy
authors.initials: R
authors.lastname: Ummels
authors.forename: Ambre
authors.initials: A
authors.lastname: Sala
authors.forename: Samer
authors.initials: S
authors.lastname: Sakr
authors.forename: Wilbert
authors.initials: W
authors.lastname: Bitter
authors.forename: Pierre
authors.initials: P
authors.lastname: Genevaux
mesh_terms: D000992:Antitoxins; D001426:Bacterial Proteins / Q000502:physiology*; D001427:Bacterial Toxins; D005798:Genes, Bacterial; D018832:Molecular Chaperones / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D013312:Stress, Physiological
chemical_list: D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D018832:Molecular Chaperones; C057842:SecB protein, Bacteria