Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv.
OBJECTIVE
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.


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.


CONCLUSIONS
The use of transposon mutants is a new functional genomic approach for the eventual definition of the mycobacterial 'lipidome'.
Waddell
S J
SJ
Department of Cellular and Molecular Medicine, St George's Hospital Medical School, London, UK.
Chung
G A
GA
Gibson
K J C
KJ
Everett
M J
MJ
Minnikin
D E
DE
Besra
G S
GS
Butcher
P D
PD
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000217:Acyltransferases / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D020868:Gene Silencing; D005798:Genes, Bacterial / Q000235:genetics; D008055:Lipids / Q000032:analysis* / Q000096:biosynthesis; D005810:Multigene Family / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics*
D018528:ATP-Binding Cassette Transporters; D004251:DNA Transposable Elements; C474312:DrrB protein, Mycobacterium tuberculosis; D008055:Lipids; C008901:phthiocerol dimycocerosate; D048630:Polyketide Synthases; D000217:Acyltransferases; C020141:flavanone synthetase; D010170:Palmitoyl-CoA Hydrolase