The W-Beijing lineage of Mycobacterium tuberculosis overproduces triglycerides and has the DosR dormancy regulon constitutively upregulated

TitleThe W-Beijing lineage of Mycobacterium tuberculosis overproduces triglycerides and has the DosR dormancy regulon constitutively upregulated
Publication TypeJournal Article
Year of Publication2007
AuthorsReed MB, Gagneux S, Deriemer K, Small PM, Barry, C. E. 3rd
JournalJ Bacteriol
Volume189
Pagination2583-9
Date PublishedApr
PubMed Central IDPMC1855800
PMID17237171
Keywords*Gene Expression Regulation, Bacterial, Animals, China, DNA Primers, Glycolipids/toxicity, Humans, Mice, Mycobacterium tuberculosis/*genetics/isolation &, purification/*metabolism/pathogenicity, Rabbits, Regulon/*genetics, Reverse Transcriptase Polymerase Chain Reaction, RNA, Bacterial/genetics/isolation & purification, Triglycerides/*metabolism, Tuberculosis
AbstractThe 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.

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