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'.
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'.
Authors: Olivia Vergnolle; Sivagami Sundaram Chavadi; Uthamaphani R Edupuganti; Poornima Mohandas; Catherine Chan; Julie Zeng; Mykhailo Kopylov; Nicholas G Angelo; J David Warren; Clifford E Soll; Luis E N Quadri Journal: J Bacteriol Date: 2015-01-05 Impact factor: 3.490
Authors: Meghan A Kirksey; Anna D Tischler; Roxane Siméone; Katherine B Hisert; Swapna Uplekar; Christophe Guilhot; John D McKinney Journal: Infect Immun Date: 2011-05-16 Impact factor: 3.441
Authors: Sivagami Sundaram Chavadi; Uthamaphani R Edupuganti; Olivia Vergnolle; Itrat Fatima; Shaneen M Singh; Clifford E Soll; Luis E N Quadri Journal: J Biol Chem Date: 2011-05-18 Impact factor: 5.157
Authors: Kuppan Gokulan; Seán E O'Leary; William K Russell; David H Russell; Mallikarjun Lalgondar; Tadhg P Begley; Thomas R Ioerger; James C Sacchettini Journal: J Biol Chem Date: 2013-04-24 Impact factor: 5.157