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

    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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