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Mechanisms of vancomycin resistance in Staphylococcus aureus
Open accessAbstract
Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive bacterial infections. Traditionally, it has been used as a drug of last resort; however, clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) strains with decreased susceptibility to vancomycin (vancomycin intermediate-resistant S. aureus [VISA]) and more recently with high-level vancomycin resistance (vancomycin-resistant S. aureus [VRSA]) have been described in the clinical literature. The rare VRSA strains carry transposon Tn1546, acquired from vancomycin-resistant Enterococcus faecalis, which is known to alter cell wall structure and metabolism, but the resistance mechanisms in VISA isolates are less well defined. Herein, we review selected mechanistic aspects of resistance in VISA and summarize biochemical studies on cell wall synthesis in a VRSA strain. Finally, we recapitulate a model that integrates common mechanistic features of VRSA and VISA strains and is consistent with the mode of action of vancomycin.
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“Phenotypically, hVISA/VISA strains exhibit distinct metabolic characteristics that may include i) increase in fructose utilization, ii) increased fatty acid metabolism, iii) impaired acetate metabolism and tricarboxylic acid cycle, iv) decrease in glutamate availability, and iv) increase expression of cell wall synthesis genes.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [104]
In the citing paper
“However, the available evidence shows that the regulatory systems most consistently implicated in this mechanism of resistance are YycFG (WalKR), VraSR (homolog of LiaFSR), and GraRS (104).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [104]
In the citing paper
“These global homeostatic changes appear to lead to a reduced autolytic activity with thickened cell wall and an increase amount of free D-Ala-D-Ala dipeptides with less peptidoglycan cross-linking (101, 104).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [104]
In the citing paper
“In addition, VISA strains bind vancomycin more avidly than their non –VISA counterparts, however, diffusion of the antibiotic molecule into the inner part of the cell wall appears to be impaired.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [104]
In the citing paper
“Finally, a striking feature of many hVISA/VISA strains is the ability to revert from one phenotype to another (or even to a fully vancomycin susceptible phenotype) in the absence of vancomycin exposure.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [104]
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Metadata
- Authors
- Gardete, S., & Tomasz, A.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- Tomasz, Alexander
- Venue
- Journal of Clinical Investigation
- Published
- 2014-07-01
- Volume
- 124
- Issue
- 7
- Pages
- 2836-2840
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4071404
- OpenAlex
- W1983784984
- Cited by
- 565
- References
- 66
- Citations by year
- 2026: 26 · 2025: 53 · 2024: 71 · 2023: 48 · 2022: 53 · 2021: 57 · 2020: 49 · 2019: 66 · 2018: 40 · 2017: 43 · 2016: 29 · 2015: 25 · 2014: 4
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (2 R01 AI457838-14)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- vancomycin resistance, Staphylococcus aureus, vancomycin-intermediate Staphylococcus aureus, vancomycin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Tn1546 transposon, vancomycin-resistant Enterococcus faecalis, cell wall biosynthesis, glycopeptides, antibiotic resistance mechanisms, cell wall metabolism
- MeSH terms
- Cell Wall, DNA Transposable Elements, DNA, Bacterial, Genes, Bacterial, Humans, Microbial Sensitivity Tests, Models, Biological, Mutation, Staphylococcal Infections, Staphylococcus aureus, Virulence, Vancomycin Resistance, Methicillin-Resistant Staphylococcus aureus
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