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Linezolid Resistance in Sequential Staphylococcus aureus Isolates Associated with a T2500A Mutation in the 23S rRNA Gene and Loss of a Single Copy of rRNA
Abstract
Linezolid is an important therapeutic option for infections caused by resistant gram-positive bacteria. We report the characterization of sequential methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates that developed resistance in a patient treated with a prolonged course of linezolid. Analysis of this series of clinical MRSA isolates detected, in the resistant isolates, the presence of a T2500A mutation in the domain V region of the 23S rRNA gene. In addition, the loss of a single copy of the 23S rRNA gene was found in 2 of the resistant isolates. As a result of these 2 factors, the proportion of mutant : wild-type 23S rRNA genes increased in association with an increase in the minimum inhibitory concentration of linezolid. The most recent isolate of this series was recovered 7 months after the patient discontinued linezolid and demonstrated reversion to a susceptible phenotype associated with a loss of the T2500A mutation.
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“Among strains isolated from clinical cases, the G2576U mutation (G2576T in rDNA) appears to be the most significant. This mutation has been found in single S. aureus strains [95,96].”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [96]
In the citing paper
“In one linezolid-resistant S. aureus strain another mutation of the rrl5 gene, namely T2500A, was found, in the absence of G2576U, G2447T mutations were also described [75,96].”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [96]
In the citing paper
“It was found that for four resistant clinical isolates of S. aureus, characterized by linezolid MIC values of 16 mg/L (three strains) and 8 mg/L (one strain), the G2576T mutation was always present in two alleles out of five, with copy 5 (rrn5) always present [96].”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [96]
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Citations
Cited by
Antibiotic resistance and its cost: is it possible to reverse resistance?
Andersson, D. I., & Hughes, D. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2319 · Cited by 2,294
David, M. Z., & Daum, R. S. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00081-09 · Cited by 1,972
Antibiotic Resistance and the MRSA Problem
Vestergaard, M., Frees, D., & Ingmer, H. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.gpp3-0057-2018 · Cited by 490
Persistence of antibiotic resistance in bacterial populations
Andersson, D. I., & Hughes, D. (2011) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2011.00289.x · Cited by 435
The emergence of antibiotic resistance by mutation
Woodford, N., & Ellington, M. J. (2007) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2006.01492.x · Cited by 417
Metadata
- Authors
- Meka, V. G., Pillai, S. K., Sakoulas, G., Wennersten, C., Venkataraman, L., DeGirolami, P. C., Eliopoulos, G. M., Moellering, Jr., & Gold, H. S.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-15
- Volume
- 190
- Issue
- 2
- Pages
- 311-317
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2144908107
- Cited by
- 247
- References
- 0
- FWCI
- 11.86
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Linezolid Resistance in Sequential Staphylococcus aureus Isolates Associated with a T2500A Mutation in the 23S rRNA Gene and Loss of a Single Copy of rRNA. https://app.cochat.ai/papers/10.1086/421471
- The paper
- Meka, V. G., Pillai, S. K., Sakoulas, G., Wennersten, C., Venkataraman, L., DeGirolami, P. C., Eliopoulos, G. M., Moellering, Jr., & Gold, H. S. (2004). Linezolid Resistance in Sequential Staphylococcus aureus Isolates Associated with a T2500A Mutation in the 23S rRNA Gene and Loss of a Single Copy of rRNA. The Journal of Infectious Diseases. https://doi.org/10.1086/421471
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.