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

Min Xie; Uday S. Ganapathy; Tian Lan; Paulina Osiecki; Jansy P. Sarathy; Véronique Dartois; Courtney C. Aldrich; Thomas Dick

doi:10.1128/aac.00381-23

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

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

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Journal	Antimicrobial agents and chemotherapy
Volume	67
Issue number	9
DOIs	https://doi.org/10.1128/aac.00381-23
State	Published - Sep 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Xie et al.

Keywords

ADP-ribosylase
NTM
caseum
drug tolerance
non-tuberculous mycobacteria
persistence
rifamycins

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

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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language = "English (US)",

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AU - Xie, Min

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AU - Lan, Tian

AU - Osiecki, Paulina

AU - Sarathy, Jansy P.

AU - Dartois, Véronique

AU - Aldrich, Courtney C.

AU - Dick, Thomas

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KW - NTM

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KW - drug tolerance

KW - non-tuberculous mycobacteria

KW - persistence

KW - rifamycins

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

Abstract

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Keywords

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