title: Reduced glutathione is required for pertussis toxin secretion by Bordetella pertussis.
abstract: The abilities of cysteine-containing compounds to support growth of Bordetella pertussis and influence pertussis toxin transcription, assembly, and secretion were examined. Cysteine is an essential amino acid for B. pertussis and must be present for protein synthesis and bacterial growth. However, cysteine can be metabolized to sulfate, and high concentrations of sulfate can selectively inhibit transcription of the virulence factors, including pertussis toxin, via the BvgAS two-component regulatory system in a process called modulation. In addition, pertussis toxin possesses several disulfide bonds, and the cysteine-containing compound glutathione can influence oxidation-reduction reactions and perhaps disulfide bond formation. Bacterial growth was not observed in the absence of a source of cysteine. Oxidized glutathione, as a sole source of cysteine, also did not support bacterial growth. Cysteine, cystine, and reduced glutathione did support bacterial growth, and none of these compounds caused modulation at the concentrations tested. Similar amounts of periplasmic pertussis toxin were detected regardless of the source of cysteine; however, in the absence of reduced glutathione, pertussis toxin was not efficiently secreted. Addition of the reducing agent dithiothreitol was unable to compensate for the lack of reduced glutathione and did not promote secretion of pertussis toxin. These results suggest that reduced glutathione does not affect the accumulation of assembled active pertussis toxin in the periplasm but plays a role in efficient pertussis toxin secretion by the bacterium.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524, USA.
authors.forename: Trevor H
authors.initials: TH
authors.lastname: Stenson
authors.forename: Angela K
authors.initials: AK
authors.lastname: Patton
authors.forename: Alison A
authors.initials: AA
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001886:Bordetella pertussis / Q000254:growth & development / Q000472:pathogenicity*; D016466:CHO Cells; D006224:Cricetinae; D003545:Cysteine / Q000502:physiology; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000502:physiology*; D009876:Operon; D010084:Oxidation-Reduction; D037342:Pertussis Toxin / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D037342:Pertussis Toxin; D005978:Glutathione; D003545:Cysteine; D004229:Dithiothreitol