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• W2915001677 abstract "Abstract There is an urgent need to develop new drugs against tuberculosis. In particular, it is critical to target drug tolerant Mycobacterium tuberculosis ( M . tuberculosis ), responsible, in part, for the lengthy antibiotic regimen required for treatment. We previously postulated that the presence of in vivo biofilm-like communities of M . tuberculosis could contribute to this drug tolerance. Consistent with this hypothesis, certain 2-aminoimidazole (2-AIs) molecules with anti-biofilm activity were shown to revert mycobacterial drug tolerance in an in vitro M . tuberculosis biofilm model. While exploring their mechanism of action, it was serendipitously observed that these 2-AI molecules also potentiated β-lactam antibiotics by affecting mycobacterial protein secretion and lipid export. As these two bacterial processes are energy-dependent, herein it was evaluated if 2-AI compounds affect mycobacterial bioenergetics. At low concentrations, 2B8, the lead 2-AI compound, collapsed both components of the proton motive force, similar to other cationic amphiphiles. Interestingly, however, the minimum inhibitory concentration of 2B8 against M . tuberculosis correlated with a higher drug concentration determined to interfere with the mycobacterial electron transport chain. Collectively, this study elucidates the mechanism of action of 2-AIs against M . tuberculosis , providing a tool to better understand mycobacterial bioenergetics and develop compounds with improved anti-mycobacterial activity." @default.
• W2915001677 created "2019-02-21" @default.
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• W2915001677 date "2019-02-06" @default.
• W2915001677 modified "2023-10-16" @default.
• W2915001677 title "2-aminoimidazoles collapse mycobacterial proton motive force and block the electron transport chain" @default.
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• W2915001677 doi "https://doi.org/10.1038/s41598-018-38064-7" @default.
• W2915001677 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6365497" @default.
• W2915001677 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30728417" @default.
• W2915001677 hasPublicationYear "2019" @default.
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