TY - JOUR
T1 - Dual Inhibition of Mycobacterial Fatty Acid Biosynthesis and Degradation by 2-Alkynoic Acids
AU - Morbidoni, Hector R.
AU - Vilchèze, Catherine
AU - Kremer, Laurent
AU - Bittman, Robert
AU - Sacchettini, James C.
AU - Jacobs, William R.
N1 - Funding Information:
H.R.M. is a Career Investigator of Consejo de Investigaciones de la Universidad Nacional de Rosario (CIURN), Argentina. This work was supported by National Institutes of Health grant AI43268. L.K. is supported by a grant from the Centre National de la Recherche Scientifique (Actions Thématiques et Incitatives sur Programmes Microbiologie Fondamentale).
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
KW - CHEMBIO
KW - MICROBIO
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U2 - 10.1016/j.chembiol.2006.01.005
DO - 10.1016/j.chembiol.2006.01.005
M3 - Article
C2 - 16638535
AN - SCOPUS:33646093721
SN - 2451-9448
VL - 13
SP - 297
EP - 307
JO - Cell Chemical Biology
JF - Cell Chemical Biology
IS - 3
ER -