New insights on Ethambutol targets in Mycobacterium tuberculosis.

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New insights on Ethambutol targets in Mycobacterium tuberculosis.

Infect Disord Drug Targets. 2018 Jan 24;:

Authors: Ghiraldi-Lopes LD, Campanerut-Sa PAZ, Evaristo GPC, Meneguello JE, Fiorini A, Baldin VP, de Souza EM, de Lima Scodro RB, Siqueira VLD, Cardoso RF

Abstract
BACKGROUND: In recent years, very few effective drugs against Mycobacterium tuberculosis (M. tb) have emerged which motivates the research with drugs already used in the treatment of tuberculosis. EMB is a bacteriostatic drug that affects cell wall integrity, but the effects of this drug on bacilli are not fully exploited.
OBJECTIVE: Based on the need to better investigate the complex mechanism of action of EMB, our study presented the proteome profile of M. tb after different times of EMB exposure, aiming to comprehend the dynamics of bacilli response to its effects.
METHOD: M. tb was exposed to subinhibitory concentration of EMB for 24 h and 48 h. The proteins were identified by MALDI- TOF/TOF.
RESULTS: The main protein changes occurred in metabolic proteins as dihydrolipoyl dehydrogenase [LpdC] (Rv0462), glutamine synthetase1 [GlnA1] (Rv2220), electron transfer flavoprotein subunit beta [ETF-β] (Rv3029c) and adenosylhomocysteinase [SahH] (Rv3248c).
CONCLUSION: Considering the functions of these proteins our results support that the intermediary metabolism and respiration were affected by EMB and this disturbance provided proteins that could be explored as additional targets for this drug.

PMID: 29366429 [PubMed - as supplied by publisher]

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