title: The W-Beijing lineage of Mycobacterium tuberculosis overproduces triglycerides and has the DosR dormancy regulon constitutively upregulated.
abstract: The Beijing family of Mycobacterium tuberculosis strains has been associated with epidemic spread and an increased likelihood of developing drug resistance. The characteristics that predispose this family to such clinical outcomes have not been identified, although one potential candidate, the phenolic glycolipid PGL-tb, has been shown to mediate a fulminant lethal disease in mice and rabbits due to lipid-mediated immunosuppression. However, PGL-tb is not uniformly expressed throughout the Beijing lineage and may not be the only unique virulence trait associated with this family. In an attempt to define phenotypes common to all Beijing strains, we interrogated a carefully selected set of isolates representing the five extant lineages of the Beijing family. Comparison of lipid production in this set revealed that all Beijing strains accumulated large quantities of triacylglycerides in in vitro aerobic culture. This accumulation was found to be coincident with upregulation of Rv3130c, whose product was previously characterized as a triacylglyceride synthase. Rv3130c is a member of the DosR-controlled regulon of M. tuberculosis, and further examination revealed that several members of this regulon were upregulated throughout this strain family. The upregulation of the DosR regulon may confer an adaptive advantage for growth in microaerophilic or anaerobic environments encountered by the bacillus during infection and thus may be related to the epidemiological phenomena associated with this important strain lineage.
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal General Hospital, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4. michael.reed@mcgill.ca
authors.forename: Michael B
authors.initials: MB
authors.lastname: Reed
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.forename: Kathryn
authors.initials: K
authors.lastname: Deriemer
authors.forename: Peter M
authors.initials: PM
authors.lastname: Small
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D000818:Animals; D002681:China; D017931:DNA Primers; D015964:Gene Expression Regulation, Bacterial; D006017:Glycolipids / Q000633:toxicity; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity; D012329:RNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D011817:Rabbits; D018085:Regulon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism*; D014376:Tuberculosis
chemical_list: D017931:DNA Primers; D006017:Glycolipids; C085331:PGL-tb-K phenolic glycolipid; D012329:RNA, Bacterial; D014280:Triglycerides