Ribosomal protection as a linezolid resistance mechanism in Mycobacterium abscessus

Tobias Funck; Kerry McGowen; Mark R. Sullivan; Samuel Zinga; Ian D. Wolf; Dennis Nurjadi; Claudia M. Denkinger; Eric J. Rubin

doi:10.1128/aac.01605-25

Ribosomal protection as a linezolid resistance mechanism in Mycobacterium abscessus

Tobias Funck, Kerry McGowen, Mark R. Sullivan, Samuel Zinga, Ian D. Wolf, Dennis Nurjadi, Claudia M. Denkinger, Eric J. Rubin^*

^*Corresponding author for this work

Abstract

Mycobacterium abscessus has emerged as a significant pulmonary pathogen characterized by its resistance to most first-line antimycobacterial drugs. Recent investigations have highlighted the clinical efficacy of including the oxazolidinone antibiotic linezolid in M. abscessus combination therapies, despite moderate resistance frequently being observed in patient isolates. Even with the potential usefulness of linezolid, the mechanisms that drive linezolid resistance in M. abscessus remain poorly understood. In several bacterial pathogens, including Mycobacterium tuberculosis, ATP-binding cassette (ABC) family proteins of the F subtype (ABC-F) have been found to confer antibiotic resistance to ribosome-targeting antibiotics, including linezolid. Here, we identified an M. abscessus ABC-F protein, MAB_2736c, that causes specific resistance to antibiotics that bind the 50S ribosomal subunit, including linezolid, macrolides, and chloramphenicol. These results demonstrate that targeting ABC-F proteins could help combat intrinsic resistance to several ribosome-targeting antibiotics in mycobacteria.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	70
Issue number	4
ISSN	0066-4804
DOIs	https://doi.org/10.1128/aac.01605-25
Publication status	Published - 04.2026

Funding

T.F. was supported by a Boehringer Ingelheim Fonds MD fellowship. M.R.S. received support as a Merck Fellow of the Damon Runyon Cancer Research Foundation, DRG-2415-20. S.Z. was supported by award numbers T32GM145407, T32GM007753, and T32GM144273 from NIGMS and award number F30AI188797 from NIAID. E.J.R. was supported by NIH/NIAID under award number R01AI179642. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, or the National Institutes of Health.

Funders	Funder number
National Institute of Allergy and Infectious Diseases
Boehringer Ingelheim Fonds	T32GM145407, T32GM007753, T32GM144273
Damon Runyon Cancer Research Foundation	DRG-2415-20
National Institutes of Health	R01AI179642
National Institute of General Medical Sciences	F30AI188797

UN SDGs

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

SDG 3 Good Health and Well-being

Access to Document

10.1128/aac.01605-25

Cite this

@article{db44d69b15544ce8ae8d1e8013f3ac12,

title = "Ribosomal protection as a linezolid resistance mechanism in Mycobacterium abscessus",

abstract = "Mycobacterium abscessus has emerged as a significant pulmonary pathogen characterized by its resistance to most first-line antimycobacterial drugs. Recent investigations have highlighted the clinical efficacy of including the oxazolidinone antibiotic linezolid in M. abscessus combination therapies, despite moderate resistance frequently being observed in patient isolates. Even with the potential usefulness of linezolid, the mechanisms that drive linezolid resistance in M. abscessus remain poorly understood. In several bacterial pathogens, including Mycobacterium tuberculosis, ATP-binding cassette (ABC) family proteins of the F subtype (ABC-F) have been found to confer antibiotic resistance to ribosome-targeting antibiotics, including linezolid. Here, we identified an M. abscessus ABC-F protein, MAB\_2736c, that causes specific resistance to antibiotics that bind the 50S ribosomal subunit, including linezolid, macrolides, and chloramphenicol. These results demonstrate that targeting ABC-F proteins could help combat intrinsic resistance to several ribosome-targeting antibiotics in mycobacteria.",

author = "Tobias Funck and Kerry McGowen and Sullivan, \{Mark R.\} and Samuel Zinga and Wolf, \{Ian D.\} and Dennis Nurjadi and Denkinger, \{Claudia M.\} and Rubin, \{Eric J.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2026 Funck et al.",

year = "2026",

month = apr,

doi = "10.1128/aac.01605-25",

language = "English",

volume = "70",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "4",

}

TY - JOUR

T1 - Ribosomal protection as a linezolid resistance mechanism in Mycobacterium abscessus

AU - Funck, Tobias

AU - McGowen, Kerry

AU - Sullivan, Mark R.

AU - Zinga, Samuel

AU - Wolf, Ian D.

AU - Nurjadi, Dennis

AU - Denkinger, Claudia M.

AU - Rubin, Eric J.

PY - 2026/4

Y1 - 2026/4

N2 - Mycobacterium abscessus has emerged as a significant pulmonary pathogen characterized by its resistance to most first-line antimycobacterial drugs. Recent investigations have highlighted the clinical efficacy of including the oxazolidinone antibiotic linezolid in M. abscessus combination therapies, despite moderate resistance frequently being observed in patient isolates. Even with the potential usefulness of linezolid, the mechanisms that drive linezolid resistance in M. abscessus remain poorly understood. In several bacterial pathogens, including Mycobacterium tuberculosis, ATP-binding cassette (ABC) family proteins of the F subtype (ABC-F) have been found to confer antibiotic resistance to ribosome-targeting antibiotics, including linezolid. Here, we identified an M. abscessus ABC-F protein, MAB_2736c, that causes specific resistance to antibiotics that bind the 50S ribosomal subunit, including linezolid, macrolides, and chloramphenicol. These results demonstrate that targeting ABC-F proteins could help combat intrinsic resistance to several ribosome-targeting antibiotics in mycobacteria.

AB - Mycobacterium abscessus has emerged as a significant pulmonary pathogen characterized by its resistance to most first-line antimycobacterial drugs. Recent investigations have highlighted the clinical efficacy of including the oxazolidinone antibiotic linezolid in M. abscessus combination therapies, despite moderate resistance frequently being observed in patient isolates. Even with the potential usefulness of linezolid, the mechanisms that drive linezolid resistance in M. abscessus remain poorly understood. In several bacterial pathogens, including Mycobacterium tuberculosis, ATP-binding cassette (ABC) family proteins of the F subtype (ABC-F) have been found to confer antibiotic resistance to ribosome-targeting antibiotics, including linezolid. Here, we identified an M. abscessus ABC-F protein, MAB_2736c, that causes specific resistance to antibiotics that bind the 50S ribosomal subunit, including linezolid, macrolides, and chloramphenicol. These results demonstrate that targeting ABC-F proteins could help combat intrinsic resistance to several ribosome-targeting antibiotics in mycobacteria.

UR - https://www.scopus.com/pages/publications/105034870303

U2 - 10.1128/aac.01605-25

DO - 10.1128/aac.01605-25

M3 - Journal articles

C2 - 41770215

AN - SCOPUS:105034870303

SN - 0066-4804

VL - 70

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 4

ER -

Ribosomal protection as a linezolid resistance mechanism in Mycobacterium abscessus

Abstract

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this