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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]
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“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]
Citations
Cites
DNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572
Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically
Ferraro, M. J. (2000) · Cited by 16,875
Tenover, F. C., Arbeit, R. D., Goering, R. V., Mickelsen, P. A., Murray, B. E., Persing, D. H., & Swaminathan, B. (1995) · Journal of Clinical Microbiology · doi:10.1128/jcm.33.9.2233-2239.1995 · Cited by 8,203
Self-citationBad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America
Boucher, H. W., Talbot, G. H., Bradley, J. S., Edwards, J. E., Gilbert, D. N., Rice, L. B., Scheld, M., Spellberg, B. J., & Bartlett, J. (2008) · Clinical Infectious Diseases · doi:10.1086/595011 · Cited by 5,092
Clinical and Laboratory Standards Institute
Gressner, A. M., & Arndt, T. (2019) · Springer Reference Medizin · doi:10.1007/978-3-662-48986-4_300416 · Cited by 5,092
Hidron, A. I., Edwards, J. R., Patel, J., Horan, T. C., Sievert, D. M., Pollock, D. A., Fridkin, S. K., & National Healthcare Safety Network Team and Participating National Healthcare Safety Network Facilities (2008) · Infection Control & Hospital Epidemiology · doi:10.1086/591861 · Cited by 3,724
Dutka‐Malen, S., Evers, S., & Courvalin, P. M. (1995) · Journal of Clinical Microbiology · doi:10.1128/jcm.33.1.24-27.1995 · Cited by 1,406
Antibiotic-Resistant Bugs in the 21st Century — A Clinical Super-Challenge
Arias, C. A., & Murray, B. E. (2009) · New England Journal of Medicine · doi:10.1056/nejmp0804651 · Cited by 1,035
Self-citationIn vitro susceptibility studies of vancomycin-resistant Enterococcus faecalis
Sahm, D. F., Kissinger, J. C., Gilmore, M. S., Murray, P. R., Mulder, R., Solliday, J., & Clarke, B. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.9.1588 · Cited by 497
Murray, B. E., Singh, K. V., Heath, J. D., Sharma, B. R., & Weinstock, G. M. (1990) · Journal of Clinical Microbiology · doi:10.1128/jcm.28.9.2059-2063.1990 · Cited by 487
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- bioMerieux. 2009. Etest daptomycin. bioMerieux, Inc., Durham, NC.
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Items 101–117 of 117
Shah, S., Bandali, A., Pontiggia, L., & Bias, T. E. (2020) · Infectious Diseases in Clinical Practice · doi:10.1097/ipc.0000000000000837 · Cited by 1
“LiaFSR is a 3-component regulatory system that allows for gram-positive bacterial cell envelope response to antibiotics and genes encoding for crucial proteins necessary for daptomycin susceptibility.(16,30) These mutations have been shown to exist more commonly in E.”
BackgroundInfluentialFernández-Alonso, J. A., Pedrosa-Corral, I., Franco-Acosta, A., Ruíz, M. E., Aznarte-Padial, P., Navarro‐Marí, J. M., & Fernández, J. G. (2023) · ANALES RANM · doi:10.32440/ar.2023.140.03.rev06 · Cited by 1
Lewis, J. D., Barros, A. J., & Sifri, C. D. (2018) · Transplant Infectious Disease · doi:10.1111/tid.13028 · Cited by 1
Avery, L. M., Kuti, J. L., Weisser, M., Egli, A., Rybak, M. J., Zasowski, E. J., Arias, C. A., Contreras, G., Chong, P. P., Aitken, S. L., et al. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciz081 · Cited by 1
Self-citationMorley, V. J., Sim, D. G., Penkevich, A., Woods, R. J., & Read, A. F. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.25.493495 · Cited by 1
“The three-component LiaFSR system 256 regulates the cellular envelope stress response, which impacts daptomycin susceptibility [25].”
BackgroundAntibiotic resistance in Enterococcus faecium clinical
Cattoir, V., & Giárd, J.-C. (2014)
Origin ofde novodaptomycin non susceptible enterococci
Kelesidis, T. (2015) · World Journal of Clinical Infectious Diseases · doi:10.5495/wjcid.v5.i2.30 · Cited by 1
Smith, J. R., Claeys, K. C., Zasowski, E. J., Yim, J., & Rybak, M. J. (2017) · Springer eBooks · doi:10.1007/978-3-319-46718-4_21
Zeng, W., Chen, T., Wu, Q., Xu, Y., Yu, K., Zhang, Y., Liu, S., Cao, J., & Zhou, T. (2020) · doi:10.21203/rs.3.rs-116663/v1
“Genes were ampli ed with speci c primers [17, 18]: (i) LiaFSR three-component regulatory system encoding gene liaF, liaS and liaR; (ii) YycFG two-component regulatory system encoding gene yycF and yycG.”
BackgroundMethod(2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu533
Saturated fatty acids enhance daptomycin activity in a Fak-dependent manner in enterococci
Maharjan, S., Getty, T. A., Dickens, Q., Hughes, A. L., Rundle, J., & Fozo, E. M. (2026) · Microbiology · doi:10.1099/mic.0.001751
“The determination of the minimal inhibitory concentration, MICs, was via broth dilution with modifications [40, 41].”
Patel, K., Chavan, M., Shah, J., & Chatterjee, S. (2026) · Archives of Microbiology · doi:10.1007/s00203-026-05077-0
Overview of the ASM-IISc Symposium on the One Health Approach to AMR in Bengaluru, India
Anand, A., Matange, N., Pande, S., & Bhandari, V. (2026) · mSphere · doi:10.1128/msphere.00211-26
“…Arias, from Houston Methodist Hospital and editor in chief of Antimicrobial Agents and Chemother apy , demonstrated how daptomycin resistance arises through cell envelope remodeling mediated by the LiaFSR system, which also introduces collateral sensitivity tradeoffs to other antibiotics (14).”
Ouancharee, W., Saleah, S., Pomwised, R., Chukamnerd, A., Surachat, K., Soontarach, R., Singkhamanan, K., & Chusri, S. (2026) · Antibiotics · doi:10.3390/antibiotics15090867
“Although its significance remains unknown, a nearby LiaS H264Q substitution has been reported within the predicted ATP-binding domain in an E. faecium isolate with reduced DAP susceptibility [46], warranting further investigation of S260G.”
Gomes, E., Figueiredo, R. J., Mesquita, J. R., Almeida, C., Araújo, D., Azevedo, N. F., & Castro, J. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1924354
“…vancomycin susceptibility in Staphylococcus aureus may involve VraSR-or WalKR-associated cell-wall remodeling, whereas reduced daptomycin susceptibility in Staphylococcus and Enterococcus may involve mprF , cls , dltABCD , or liaFSR (Munita et al., 2012; Diaz et al., 2014; Baek et al., 2017).”
Matlapudi, D. P., Kewalramani, A., Mitchell, K., Kidney, A., Wahl, K., Prussing, C., Haas, W., & Quale, J. M. (2026) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2026.109208
Foster, R. A., Cluck, D. B., Rogers, D. J., White, B. P., Daut, L., Bland, C. M., Webb, B. J., Henao‐Martínez, A. F., & Chastain, D. B. (2026) · Therapeutic Advances in Infectious Disease · doi:10.1177/20499361261499816
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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