Future microbiology · 2016
Membrane-targeting AM-0016 kills mycobacterial persisters and shows low propensity for resistance development.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Mukherjee Devika, Zou Hanxun, Liu Shouping, Beuerman Roger, Dick Thomas
Аннотация
AIM: To test the hypothesis that targeting the cytoplasmic membrane may be an effective way to kill persister mycobacteria and delay the emergence of resistance.
METHODS: In vitro activity of AM-0016, a novel xanthone-based antibacterial, was assessed against growing and persister tubercle bacilli. Resistance mutation frequencies were determined. Biochemical membrane and electron microscopic analyses were carried out.
RESULTS: AM-0016 rapidly sterilized growing tubercle bacillus cultures and displayed strong bactericidal activity against persister bacteria. Spontaneous resistance mutation frequency was lower than 10(-8). Exposure to AM-0016 resulted in rapid collapse of the membrane potential. Imaging revealed deformation of the cell envelope.
CONCLUSION: Targeting the cytoplasmic membrane may be an attractive approach to eliminate persister mycobacteria and slow down the emergence of genetic drug resistance.
METHODS: In vitro activity of AM-0016, a novel xanthone-based antibacterial, was assessed against growing and persister tubercle bacilli. Resistance mutation frequencies were determined. Biochemical membrane and electron microscopic analyses were carried out.
RESULTS: AM-0016 rapidly sterilized growing tubercle bacillus cultures and displayed strong bactericidal activity against persister bacteria. Spontaneous resistance mutation frequency was lower than 10(-8). Exposure to AM-0016 resulted in rapid collapse of the membrane potential. Imaging revealed deformation of the cell envelope.
CONCLUSION: Targeting the cytoplasmic membrane may be an attractive approach to eliminate persister mycobacteria and slow down the emergence of genetic drug resistance.