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New insights on Ethambutol Targets in Mycobacterium tuberculosis

[ Vol. 19 , Issue. 1 ]

Author(s):

Luciana D. Ghiraldi-Lopes*, Paula A. Zanetti Campanerut-Sá, Geisa P. Caprini Evaristo, Jean E. Meneguello, Adriana Fiorini, Vanessa P. Baldin, Emanuel Maltempi de Souza, Regiane Bertin de Lima Scodro, Vera L.D. Siqueira and Rosilene F. Cardoso   Pages 73 - 80 ( 8 )

Abstract:


Background: In recent years, very few effective drugs against Mycobacterium tuberculosis have emerged, which motivates the research with drugs already used in the treatment of tuberculosis. Ethambutol 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 ethambutol, our study presented the proteome profile of M. tuberculosis after different times of ethambutol exposure, aiming to comprehend the dynamics of bacilli response to its effects. M. tuberculosis was exposed to ½ MIC of ethambutol at 24 and 48 hours. The proteins were identified by MALDI-TOF/TOF.

Results: The main protein changes occurred in metabolic proteins as dihydrolipoyl dehydrogenase (Rv0462), glutamine synthetase1 (Rv2220), electron transfer flavoprotein subunit beta (Rv3029c) and adenosylhomocysteinase (Rv3248c).

Conclusion: Considering the functions of these proteins, our results support that the intermediary metabolism and respiration were affected by ethambutol and this disturbance provided proteins that could be explored as additional targets for this drug.

Keywords:

Mycobacterium tuberculosis, ethambutol, proteome, two-dimension gel electrophoresis, MALDI- TOF/TOF, STRING database.

Affiliation:

Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana, Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana, Laboratorio de Apoio ao Desenvolvimento Tecnologico - Instituto de Quimica, Rio de Janeiro, Rio de Janeiro, Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana, Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana, Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana, Universidade Federal do Parana - Departamento de Ciencias Biologicas, Curitiba, Parana, Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana, Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana, Universidade Estadual de Maringa - Departamento de Analises Clinicas e Biomedicina, Maringa, Parana

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