Title

Virulence attenuation of two Mas-like polyketide synthase mutants of Mycobacterium tuberculosis

Authors

Authors

C. Rousseau; T. D. Sirakova; V. S. Dubey; Y. Bordat; P. E. Kolattukudy; B. Gicquel;M. Jackson

Abbreviated Journal Title

Microbiology-(UK)

Keywords

CELL-WALL; TRANSPOSON MUTAGENESIS; GENE-CLUSTER; TREHALOSE; STRAINS; BIOSYNTHESIS; PERMEABILITY; EXPRESSION; DISRUPTION; ENVELOPE; Microbiology

Abstract

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.

Journal Title

Microbiology-Sgm

Volume

149

Publication Date

1-1-2003

Document Type

Article

Language

English

First Page

1837

Last Page

1847

WOS Identifier

WOS:000184209000023

ISSN

1350-0872

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