This Article Full Text Full Text (PDF) Other Versions of this Article: JB.01670-06v1 189/7/2583    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reed, M. B. Articles by Barry, C. E. Search for Related Content PubMed PubMed Citation Articles by Reed, M. B. Articles by Barry, C. E., III

The W-Beijing Lineage of Mycobacterium tuberculosis Overproduces Triglycerides and Has the DosR Dormancy Regulon Constitutively Upregulated

Tuberculosis Research Section, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland 20852,¹ Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California 94305,² Institute for Systems Biology, 1441 North 34th Street, Seattle, Washington 98103,³ School of Medicine, One Shields Avenue, University of California, Davis, California 95616,⁴ Bill and Melinda Gates Foundation, Seattle, Washington 98102⁵

Received 27 October 2006/ Accepted 9 January 2007

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.

Published ahead of print on 19 January 2007.

This article has been cited by other articles:

• Flores, L., Van, T., Narayanan, S., DeRiemer, K., Kato-Maeda, M., Gagneux, S. (2007). Large Sequence Polymorphisms Classify Mycobacterium tuberculosis Strains with Ancestral Spoligotyping Patterns. J. Clin. Microbiol. 45: 3393-3395 [Abstract] [Full Text]  
• Sousa, E. H. S., Tuckerman, J. R., Gonzalez, G., Gilles-Gonzalez, M.-A. (2007). DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis. Protein Sci. 16: 1708-1719 [Abstract] [Full Text]