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Cited by 118Antibiotic Resistance in BacteriaAntimicrobial Resistance in StaphylococcusBacterial Genetics and Biotechnology

Correlation between Mutations in liaFSR of Enterococcus faecium and MIC of Daptomycin: Revisiting Daptomycin Breakpoints

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Munita, Jose M., Panesso, Diana, Diaz, Lorena, Tran, Truc T., Reyes, Jinnethe, Wanger, Audrey, Murray, Barbara E., Arias, Cesar A.·2012·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.00509-12PMC PMC3421602
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Abstract

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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Crossref · 10.1128/aac.00509-12

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  • The majority (75%) of DAP-susceptible E. faecium isolates recovered from bacteremic patients whose MIC was in the higher range of susceptibility (between 3 and 4 μg/mL) harbored mutations in LiaFSR.

    “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]

  • None of the E. faecium isolates with DAP MIC ≤ 2 μg/mL exhibited changes in LiaFSR.

    “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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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)
ORCID
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
DOI
10.1128/aac.00509-12
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
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › 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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