ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerant <i>M. abscessus</i> in caseum surrogate-Reference-Cited by-同舟云学术

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

Published:2023-09-19 Issue:9 Volume:67 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Xie Min¹,Ganapathy Uday S.¹,Lan Tian²,Osiecki Paulina¹,Sarathy Jansy P.¹,Dartois Véronique¹³,Aldrich Courtney C.²,Dick Thomas¹³⁴^ORCID

Affiliation:

1. Center for Discovery and Innovation, Hackensack Meridian Health , Nutley, New Jersey, USA

2. Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota, USA

3. Department of Medical Sciences, Hackensack Meridian School of Medicine , Nutley, New Jersey, USA

4. Department of Microbiology and Immunology, Georgetown University , Washington, District of Columbia, USA

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.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/aac.00381-23

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