Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall
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The bactericidal, cell membrane–targeting lipopeptide antibiotic daptomycin (DAP) is an important agent in treating invasive Staphylococcus aureus infections. However, there have been numerous recent reports of development of daptomycin resistance (DAP‐R) during therapy with this agent. The mechanisms of DAP‐R in S. aureus appear to be quite diverse. DAP‐R strains often exhibit progressive accumulation of single nucleotide polymorphisms in the multipeptide resistance factor gene (mprF) and the yycFG components of the yycFGHI operon. Both loci are involved in key cell membrane (CM) events, with mprF being responsible for the synthesis and outer CM translocation of the positively charged phospholipid, lysyl‐phosphotidylglycerol (L‐PG), while the yyc operon is involved in the generalized response to stressors such as antimicrobials. In addition, other perturbations of the CM have been identified in DAP‐R strains, including extremes in CM order, resistance to CM depolarization and permeabilization, and reduced surface binding of DAP. Moreover, modifications of the cell wall (CW) appear to also contribute to DAP‐R, including enhanced expression of the dlt operon (involved in d‐alanylation of CW teichoic acids) and progressive CW thickening.
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A homolog of LiaFSR (VraTSR) seems to also contribute to the DAP-R phenotype mediated by changes in MprF in S. aureus.
“Of interest, a homolog of LiaFSR (VraTSR) seems to also contribute to the DAP-R phenotype mediated by changes in MprF in S. aureus (97).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [97]
YycFG (WalKR), an essential two-component regulatory system implicated in cell-wall synthesis and homeostasis, has been found to be important to DAP-R both in enterococci and S. aureus.
“For example, YycFG (WalKR), an essential two-component regulatory system that has been implicated in cell-wall synthesis and homeostasis, has been found to be important to DAP-R both in enterococci and S. aureus (96, 97).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [97]
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- Authors
- Bayer, A. S., Schneider, T., & Sahl, H.
- Affiliations
- University of California, Los Angeles (US)
- University of Bonn (DE)
- Corresponding author
- Bayer, Arnold S.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2012-12-05
- Volume
- 1277
- Issue
- 1
- Pages
- 139-158
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC3556211
- OpenAlex
- W1917119829
- Cited by
- 311
- References
- 126
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 13 · 2023: 19 · 2022: 27 · 2021: 27 · 2020: 25 · 2019: 15 · 2018: 20 · 2017: 24 · 2016: 36 · 2015: 32 · 2014: 28 · 2013: 16
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (UL1TR000124)
- U.S. Food and Drug Administration
- National Institute of Allergy and Infectious Diseases (R01-AI039108-14, R01AI039108)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- daptomycin resistance, Staphylococcus aureus, mprF, lysyl-phosphatidylglycerol, plasma membrane, cell wall, dlt operon, cell wall thickening, membrane depolarization, membrane permeabilization, lipopeptide antibiotics, antibiotic resistance mechanisms
- MeSH terms
- Anti-Bacterial Agents, Cell Wall, Humans, Staphylococcal Infections, Staphylococcus aureus, Vancomycin, Daptomycin, Antimicrobial Cationic Peptides, Drug Resistance, Bacterial
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