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

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

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
Journal	Antimicrobial Agents and Chemotherapy
Volume	67
Issue number	9
DOIs	https://doi.org/10.1128/aac.00381-23
State	Published - Sep 2023

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/aac.00381-23

Cite this

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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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author = "Min Xie and Ganapathy, {Uday S.} and Tian Lan and Paulina Osiecki and Sarathy, {Jansy P.} and V{\'e}ronique Dartois and Aldrich, {Courtney C.} and Thomas Dick",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Xie et al.",

year = "2023",

month = sep,

doi = "10.1128/aac.00381-23",

language = "English",

volume = "67",

journal = "Antimicrobial Agents and Chemotherapy",

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AU - Xie, Min

AU - Ganapathy, Uday S.

AU - Lan, Tian

AU - Osiecki, Paulina

AU - Sarathy, Jansy P.

AU - Dartois, Véronique

AU - Aldrich, Courtney C.

AU - Dick, Thomas

PY - 2023/9

Y1 - 2023/9

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AB - 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.

KW - ADP-ribosylase

KW - NTM

KW - caseum

KW - drug tolerance

KW - non-tuberculous mycobacteria

KW - persistence

KW - rifamycins

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DO - 10.1128/aac.00381-23

M3 - Article

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SN - 0066-4804

VL - 67

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 9

ER -

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

Abstract

ASJC Scopus subject areas

Keywords

UN SDGs

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