Present address: Gurdyal S. Besra, Division of Infectious Diseases, Stanford University School of Medicine, CCSR-2250, 269 Campus Drive, Stanford, CA 94305, USA.
Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv
Article first published online: 26 JAN 2005
Letters in Applied Microbiology
Volume 40, Issue 3, pages 201–206, March 2005
How to Cite
Waddell, S.J., Chung, G.A., Gibson, K.J.C., Everett, M.J., Minnikin, D.E., Besra, G.S. and Butcher, P.D. (2005), Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv. Letters in Applied Microbiology, 40: 201–206. doi: 10.1111/j.1472-765X.2005.01659.x
- Issue published online: 26 JAN 2005
- Article first published online: 26 JAN 2005
- 2004/0989: received 26 August 2004, revised and accepted 19 November 2004
- cell wall;
- Mycobacterium tuberculosis;
- polyketide synthases
Aims: Phthiocerol dimycocerosate (PDIM) waxes and other lipids are necessary for successful Mycobacterium tuberculosis infection, although the exact role of PDIM in host-pathogen interactions remains unclear. In this study, we investigated the contribution of tesA, drrB, pks6 and pks11 genes in complex lipid biosynthesis in M. tuberculosis.
Methods and Results: Four mutants were selected from M. tuberculosis H37Rv transposon mutant library. The transposon insertion sites were confirmed to be within the M. tuberculosis open reading frames for tesA (a probable thioesterase), drrB (predicted ABC transporter), pks11 (putative chalcone synthase) and pks6 (polyketide synthase). The first three of these transposon mutants were unable to generate PDIM and the fourth lacked novel polar lipids.
Conclusions: Mycobacterium tuberculosis can be cultivated in vitro without the involvement of certain lipid synthesis genes, which may be necessary for in vivo pathogenicity.
Significance and Impact of the Study: The use of transposon mutants is a new functional genomic approach for the eventual definition of the mycobacterial ‘lipidome’.