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PMID: 17237171 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

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

Journal of bacteriology ·Vol. 189 ·No. 7 ·2007-04-00 ·Pages 2583-9

Reed MB, Gagneux S, Deriemer K, Small PM, Barry CE

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.

MeSH Terms
Animals China DNA Primers Gene Expression Regulation, Bacterial Glycolipids/toxicity Humans Mice Mycobacterium tuberculosis/genetics,isolation & purification,metabolism,pathogenicity RNA, Bacterial/genetics,isolation & purification Rabbits Regulon/genetics Reverse Transcriptase Polymerase Chain Reaction Triglycerides/metabolism Tuberculosis
Chemicals
DNA Primers Glycolipids PGL-tb-K phenolic glycolipid RNA, Bacterial Triglycerides
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Reed Michael B
The Research Institute of the McGill University Health Centre, Montreal General Hospital, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4. michael.reed@mcgill.ca
Gagneux Sebastien
Deriemer Kathryn
Small Peter M
Barry Clifton E
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.01670-06
Email
michael.reed@mcgill.ca
Published
2007-04-00
Epub
2007-00-19
Pages
2583-9
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC1855800
Subset
IM
Grants
FIC NIH HHS · K01 TW000001 · United States
FIC NIH HHS · K01 TW000001-07 · United States
Intramural NIH HHS · Z01 AI000783-11 · United States
External Links
PubMed source DOI: 10.1128/JB.01670-06 PMC Full Text View journal details
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