ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerant <i>M. abscessus</i> in caseum surrogate
Min Xie, Uday S. Ganapathy, Tian Lan, Paulina Osiecki, Jansy P. Sarathy, Véronique Dartois, Courtney C. Aldrich, Thomas Dick
Abstract
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.
Topics & Concepts
RifabutinDrugMicrobiologyDrug resistancePharmacologyAntibioticsChemistryMedicineBiologyClarithromycinMycobacterium research and diagnosisClostridium difficile and Clostridium perfringens researchAntibiotic Resistance in Bacteria