Résumé
2-Hexadecynoic acid and 2-octadecynoic acid have cidal activity against
Mycobacterium smegmatis and
Mycobacterium bovis BCG. At subinhibitory concentrations,
M.
smegmatis rapidly transformed [1-
14C]-2-hexadecynoic acid into endogenous fatty acids and elongated them into mycolic acids. Toxic concentrations of 2-hexadecynoic acid resulted in accumulation of 3-ketohexadecanoic acid, which blocked fatty acid biosynthesis, and 3-hexadecynoic acid, an inhibitor of fatty acid degradation. The combination of these two metabolites is necessary to achieve the inhibition of
M.
smegmatis. We conclude that 2- and 3-hexa/octadecynoic acids inhibit mycolic acid biosynthesis, fatty acid biosynthesis, and fatty acid degradation, pathways of significant importance for mycobacteria.