ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerant M. abscessus in caseum surrogate

ADP 核糖基化抗性的利福布丁类似物对干酪杆菌替代品中的耐药性脓肿分枝杆菌表现出增强的杀菌活性

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作者:Min Xie, Uday S Ganapathy, Tian Lan, Paulina Osiecki, Jansy P Sarathy, Véronique Dartois, Courtney C Aldrich, Thomas Dick

Abstract

Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary Mycobacterium abscessus disease is associated with poor treatment outcomes. In caseum surrogate, M. abscessus entered an extended stationary phase showing tolerance to killing by most current antibiotics, suggesting that caseum persisters contribute to the poor performance of available treatments. Novel ADP-ribosylation-resistant rifabutin analogs exhibited bactericidal activity against these M. abscessus persisters at concentrations achievable by rifamycins in caseum.

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