title: Functional genomics reveals the sole sulphate transporter of the Mycobacterium tuberculosis complex and its relevance to the acquisition of sulphur in vivo.
abstract: Sulphur is essential for some of the most vital biological activities such as translation initiation and redox maintenance, and genes involved in sulphur metabolism have been implicated in virulence. Mycobacterium tuberculosis has three predicted genes for the prototrophic acquisition of sulphur as sulphate: cysA, part of an ABC transporter, and cysA2 and A3, SseC sulphotransferases. Screening for amino acid auxotrophs of Mycobacterium bovis BCG, obtained by transposon mutagenesis, was used to select methionine auxotrophs requiring a sulphur-containing amino acid for growth. We have characterized one of these auxotrophs as being disrupted in cysA. Both the cysA mutant and a previously identified mutant in an upstream gene, subI, were functionally characterized as being completely unable to take up sulphate. Complementation of the cysA mutant with the wild-type gene from M. tuberculosis restored prototrophy and the ability to take up sulphate with the functional characteristics of an ABC transporter. Hence, it appears that this is the sole locus encoding inorganic sulphur transport in the M. tuberculosis complex.
authors.affiliation: Tuberculosis Research Group, Veterinary Laboratories Agency-Weybridge, New Haw, Surrey, UK.
authors.forename: Esen
authors.initials: E
authors.lastname: Wooff
authors.forename: Stephen L I
authors.initials: SL
authors.lastname: Michell
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Gordon
authors.forename: Mark A
authors.initials: MA
authors.lastname: Chambers
authors.forename: Stoyan
authors.initials: S
authors.lastname: Bardarov
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: R Glyn
authors.initials: RG
authors.lastname: Hewinson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Wheeler
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D002840:Chromates / Q000494:pharmacology; D004251:DNA Transposable Elements; D024901:Drug Resistance, Multiple, Bacterial; D005816:Genetic Complementation Test; D023281:Genomics / Q000379:methods; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002840:Chromates; D004251:DNA Transposable Elements; D013455:Sulfur; D008715:Methionine