Mycolic acid, an α-branched-β-hydroxy long chain fatty acid, is known to be the most characteristic cell wall component of acid-fast bacteria, such as
Mycobacterium, Nocardia and
Rhodococcus. Cell wall components such as cord factor containing mycolic acid show various biological activities in host immune responses. However, very little is known about the mechanism of mycolic acid biosynthesis in these bacteria. In order to reveal such mechanisms in more detail, an investigation was made of the the incorporation of various
14C-labeled precursors into molecular species of mycolic acid in
Rhodococcus ruber, a weakly acid-fast soil Actinomycetes. Further, the inhibition of mycolic acid synthesis by antituberculous agents, isonicotinic acid hydrazide (INH) and cerulenin was examined.
In the results, 1-
14C-lairic acid, 1-
14C-myristic acid or 1-
14C-palmitic acid was vigorously incorporated specifcally into the C
36, C
38 or C
40 molecular species of mycolic acids by the short-time incubation with resting cell suspension of
R. ruber. The results suggest that these fatty acids were directly incorporated into α-branched chain of mycolic acids. On the other hand, 2-
14C-acetic acid was incorporated into the C
44, C
46 and C
48 molecular species more abundantly. This finding suggests that acetic acid was incorporated into β-chain (straight chain) of the mycolic acid. A marked inhibition of mycolic acid synthesis was observed with 4-16μg/ml of INH and/or 0.25-1μg/ml of cerulenin in the cell suspension. Furthermore, co-administration of INH and cerulenin showed distinctively the synergistic inhibition of cell growth, although mycolic acid synthesis was inhibited only additively. The co-administration of such drugs may have a synergistic effect on the chemotherapy of human tuberculosis.
抄録全体を表示