Virulence attenuation of two Mas-like polyketide synthase mutants of Mycobacterium tuberculosis.
The cell envelope of pathogenic mycobacteria is highly distinctive in that it contains a large number of structurally related very long multiple methyl-branched fatty acids. These complex molecules are thought to play important roles in cell envelope organization and virulence. The genetic and enzymic characterization of the polyketide synthase Mas, which is responsible for the synthesis of one such family of fatty acids (the mycocerosic acids), paved the way towards the identification of other enzymes involved in the synthesis of methyl-branched fatty acids in M. tuberculosis. In an effort to elucidate the origin of these complex fatty acids and their possible involvement in pathogenesis, the two mas-like polyketide genes pks5 and pks7 were disrupted in M. tuberculosis and the effects of their inactivation on fatty acid composition and virulence were analysed. While the disruption of pks7 resulted in a mutant deficient in the production of phthiocerol dimycocerosates, the cell envelope composition of the pks5 mutant was found to be identical to that of the wild-type parental strain M. tuberculosis H37Rv. Interestingly, both the pks5 and pks7 mutants displayed severe growth defects in mice.
Rousseau
Cécile
C
Unité de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Sirakova
Tatiana D
TD
Biomolecular Science Center, Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL 32816-2360, USA.
Dubey
Vinod S
VS
Biomolecular Science Center, Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL 32816-2360, USA.
Bordat
Yann
Y
Unité de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Kolattukudy
Pappachan E
PE
Biomolecular Science Center, Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL 32816-2360, USA.
Gicquel
Brigitte
B
Unité de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Jackson
Mary
M
Unité de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000235:genetics; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D005798:Genes, Bacterial; D008264:Macrophages / Q000382:microbiology; D008563:Membrane Lipids / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
D004269:DNA, Bacterial; D005227:Fatty Acids; D008563:Membrane Lipids; D009097:Multienzyme Complexes