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Folate Pathway Disruption Leads to Critical Depletion of Methionine Derivatives in Mycobacterium tuberculosis

ABSTRACT: In this study, screening efforts identified novel antifolates with potent, targeted activity against whole cell Mycobacterium tuberculosis. Liquid chromatography-mass spectrometry analysis of antifolate-treated cultures revealed unique metabolic disruption, including decreased pools of methionine and S-adenosylmethionine. Transcriptomic analysis highlighted up-regulation genes involved in the biosynthesis and utilization of methionine. Supplementation with amino acids or methionine derivatives was sufficient to rescue cultures from MIC-level antifolate treatment. Instead of the “thymineless death” that characterizes folate pathway inhibition in a wide variety of organisms, these data suggest that M. tuberculosis is vulnerable to a critical disruption of the biosynthesis of methionine-derived compounds.

ORGANISM(S): Mycobacterium tuberculosis H37Rv

PROVIDER: GSE55979 | GEO | 2014/03/19

SECONDARY ACCESSION(S): PRJNA241497

REPOSITORIES: GEO

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