Waddell_et_al-2005-Letters_in_Applied_Microbiology.pdf (176.92 kB)
Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv
journal contribution
posted on 2023-06-07, 16:23 authored by Simon WaddellSimon Waddell, G A Chung, K J C Gibson, M J Everett, D E Minnikin, G S Besra, P D ButcherAims: 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’.
History
Publication status
- Published
File Version
- Published version
Journal
Letters In Applied MicrobiologyPublisher
Blackwell PublishingExternal DOI
Issue
3Volume
40Page range
201-6Department affiliated with
- Global Health and Infection Publications
Full text available
- Yes
Peer reviewed?
- Yes