title: Altered protein expression patterns of Mycobacterium tuberculosis induced by ATB107.
abstract: 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.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, PR China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shen
authors.forename: Enzhuo
authors.initials: E
authors.lastname: Yang
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Ruiliang
authors.initials: R
authors.lastname: Jin
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Xu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Honghai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005798:Genes, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D007209:Indole-3-Glycerol-Phosphate Synthase / Q000037:antagonists & inhibitors; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D020543:Proteome / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011812:Quinuclidines / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014227:Triazines / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy; D014774:Virulence
chemical_list: C534782:ATB 107; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D020543:Proteome; D011812:Quinuclidines; D014227:Triazines; D007209:Indole-3-Glycerol-Phosphate Synthase