Virulence attenuation of two Mas-like polyketide synthase mutants of Free

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 . In an effort to elucidate the origin of these complex fatty acids and their possible involvement in pathogenesis, the two -like polyketide genes and were disrupted in and the effects of their inactivation on fatty acid composition and virulence were analysed. While the disruption of resulted in a mutant deficient in the production of phthiocerol dimycocerosates, the cell envelope composition of the mutant was found to be identical to that of the wild-type parental strain H37Rv. Interestingly, both the and mutants displayed severe growth defects in mice.

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2003-07-01
2024-03-28
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