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Correlation between Mutations in liaFSR of Enterococcus faecium and MIC of Daptomycin: Revisiting Daptomycin Breakpoints
Open accessAbstract
Mutations in liaFSR , a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to 3 μg/ml (the DAP breakpoint is 4 μg/ml), suggesting that mutations in the liaFSR system could be a pivotal initial event in the development of DAP resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs between 3 and 4 μg/ml might harbor mutations in liaFSR , we studied 38 Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and 4 μg/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates had predicted amino acid changes in the LiaFSR system. Moreover, we previously showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 μg/ml), 5 had mutations in liaFSR . In contrast, none of 16 E. faecium isolates with a DAP MIC of ≤2 μg/ml harbored mutations in this system ( P < 0.0001). All but one isolate with liaFSR changes exhibited DAP MICs of ≥16 μg/ml by Etest using brain heart infusion agar (BHIA), a medium that better supports enterococcal growth. Our findings provide a strong association between DAP MICs within the upper susceptibility range and mutations in the liaFSR system. Concomitant susceptibility testing on BHIA may be useful for identifying these E. faecium first-step mutants. Our results also suggest that the current DAP breakpoint for E. faecium may need to be reevaluated.
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“Furthermore, the majority (75%) of DAP-susceptible E. faecium isolates recovered from bacteremic patients whose MIC was in the higher range of susceptibility (i.e. between 3 and 4 μg/mL) harbored mutations in LiaFSR.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [91]
In the citing paper
“Conversely, none of the isolates of the same collection with DAP MIC ≤ 2 μg/mL exhibited changes in this system (91).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [91]
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Metadata
- Authors
- Munita, J. M., Panesso, D., Diaz, L., Tran, T. T., Reyes, J., Wanger, A., Murray, B. E., & Arias, C. A.
- Affiliations
- Universidad del Desarrollo (CL)
- Universidad El Bosque (CO)
- Laboratory for Antimicrobial Research, University of Texas Medical School at Houston, Houston, Texas, USA
- University of Houston (US)
- The University of Texas Health Science Center at Houston (US)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2012-08
- Volume
- 56
- Issue
- 8
- Pages
- 4354-4359
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3421602
- OpenAlex
- W2107978429
- Cited by
- 118
- References
- 37
- Citations by year
- 2026: 8 · 2025: 3 · 2023: 6 · 2022: 12 · 2021: 2 · 2020: 12 · 2019: 4 · 2018: 12 · 2017: 8 · 2016: 17 · 2015: 12 · 2014: 13 · 2013: 7 · 2012: 2
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Repositorio Institucional Universidad El Bosque (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI093749, R00AI072961, R01 AI72961, K99AI072961)
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- daptomycin resistance, Enterococcus faecium, minimum inhibitory concentration, envelope stress response, bloodstream isolates, antimicrobial susceptibility testing
- MeSH terms
- Anti-Bacterial Agents, Bacterial Proteins, Base Sequence, Cell Wall, DNA, Bacterial, Microbial Sensitivity Tests, Mutation, Vancomycin, Enterococcus faecium, Sequence Analysis, DNA, Daptomycin, Vancomycin Resistance, Drug Resistance, Bacterial
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