New insights on Ethambutol Targets in Mycobacterium tuberculosis.
Antitubercular Agents
/ pharmacology
Bacterial Proteins
/ metabolism
Cell Wall
/ drug effects
Ethambutol
/ pharmacology
Humans
Metabolic Networks and Pathways
/ drug effects
Microbial Sensitivity Tests
/ methods
Mycobacterium tuberculosis
/ drug effects
Proteome
/ drug effects
Time Factors
Tuberculosis
/ drug therapy
MALDI- TOF/TOF
Mycobacterium tuberculosis
STRING database
ethambutol
proteome
two-dimension gel electrophoresis.
Journal
Infectious disorders drug targets
ISSN: 2212-3989
Titre abrégé: Infect Disord Drug Targets
Pays: United Arab Emirates
ID NLM: 101269158
Informations de publication
Date de publication:
2019
2019
Historique:
received:
28
06
2017
revised:
18
01
2018
accepted:
22
01
2018
pubmed:
26
1
2018
medline:
7
6
2019
entrez:
26
1
2018
Statut:
ppublish
Résumé
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. 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. The main protein changes occurred in metabolic proteins as dihydrolipoyl dehydrogenase (Rv0462), glutamine synthetase1 (Rv2220), electron transfer flavoprotein subunit beta (Rv3029c) and adenosylhomocysteinase (Rv3248c). 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 29366429
pii: IDDT-EPUB-88174
doi: 10.2174/1871526518666180124140840
doi:
Substances chimiques
Antitubercular Agents
0
Bacterial Proteins
0
Proteome
0
Ethambutol
8G167061QZ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
73-80Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.