ATB107 is a potent inhibitor of
indole-3-glycerol phosphate synthase (IGPS). It can effectively inhibit the growth of clinical isolates of
drug-resistant Mycobacterium tuberculosis strains as well as M.
tuberculosis H37Rv. To investigate the mechanism of
ATB107 action in M.
tuberculosis, two-dimensional gel electrophoresis coupled with MALDI-TOF-MS analysis (2-DE-MS) was performed to illustrate alterations in the
protein expression profile in response to
ATB107. Results show that
ATB107 affected
tryptophan biosynthesis by decreasing the expression of
protein encoded by Rv3246c, the transcriptional regulatory
protein of MtrA belonging to the MtrA-MtrB two-component regulatory system, in both
drug-sensitive and
drug-resistant virulent strains.
ATB107 might present a stress condition similar to
isoniazid (INH) or
ethionamide for M.
tuberculosis since the altered expression in response to
ATB107 of some genes, such as Rv3140, Rv2243, and Rv2428, is consistent with INH or
ethionamide treatment. After incubation with
ATB107, the expression of 2
proteins encoded by Rv0685 and Rv2624c was down-regulated while that of
protein encoded by Rv3140 was up-regulated in all M.
tuberculosis strains used in this study. This may be the common response to
tryptophan absence; however, relations to
ATB107 are unknown and further evaluation is warranted.