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Ribosomal protection as a linezolid resistance mechanism in Mycobacterium abscessus
Open accessPreprint — published as 10.1128/aac.01605-25 · Paper page
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.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Funck, T., McGowen, K., Sullivan, M. R., Zinga, S., Wolf, I. D., Nurjadi, D., Denkinger, C. M., & Rubin, E. J.
- Affiliations
- Harvard University (US)
- University Hospital Schleswig-Holstein (DE)
- University Hospital Heidelberg (DE)
- Corresponding author
- Rubin, Eric J.
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- openRxiv
- Published
- 2025-10-24
- Volume
- 70
- Issue
- 4
- Pages
- e0160525-e0160525
- ISSN
- 0066-4804 (ISSN-L)
- PMC
- PMC13041422
- OpenAlex
- W7133187841
- Cited by
- 1
- References
- 1
- Citations by year
- 2026: 1
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Damon Runyon Cancer Research Foundation (DRG-2415-20)
- Boehringer Ingelheim Fonds
- National Institutes of Health (1f30ai188797-01)
- National Institute of General Medical Sciences (T32GM145407, T32GM007753, T32GM144273, T32GM007753, T32GM145407, T32GM144273)
- National Institute of Allergy and Infectious Diseases (R01AI179642)
- Topics
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Keywords
- Mycobacterium abscessus, linezolid resistance, ribosome-targeting antibiotics, 50S ribosomal subunit, macrolides, chloramphenicol, intrinsic antibiotic resistance, oxazolidinones
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