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In Vitro Resistance of Staphylococcus aureus to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Alterations in Cytoplasmic Membrane Fluidity
Open accessAbstract
Platelet microbicidal proteins (PMPs) are small, cationic peptides which possess potent microbicidal activities against common bloodstream pathogens, such as Staphylococcus aureus. We previously showed that S. aureus strains exhibiting resistance to thrombin-induced PMP (tPMP-1) in vitro have an enhanced capacity to cause human and experimental endocarditis (T. Wu, M. R. Yeaman, and A. S. Bayer, Antimicrob. Agents Chemother. 38:729-732, 1994; A. S. Bayer et al., Antimicrob. Agents Chemother. 42:3169-3172, 1998; V. K. Dhawan et al., Infect. Immun. 65:3293-3299, 1997). However, the mechanisms mediating tPMP-1 resistance in S. aureus are not fully delineated. The S. aureus cell membrane appears to be a principal target for the action of tPMP-1. To gain insight into the basis of tPMP-1 resistance, we compared several parameters of membrane structure and function in three tPMP-1-resistant (tPMP-1(r)) strains and their genetically related, tPMP-1-susceptible (tPMP-1(s)) counterpart strains. The tPMP-1(r) strains were derived by three distinct methods: transposon mutagenesis, serial passage in the presence of tPMP-1 in vitro, or carriage of a naturally occurring multiresistance plasmid (pSK1). All tPMP-1(r) strains were found to possess elevated levels of longer-chain, unsaturated membrane lipids, in comparison to their tPMP-1(s) counterparts. This was reflected in corresponding differences in cell membrane fluidity in the strain pairs, with tPMP-1(r) strains exhibiting significantly higher degrees of fluidity as assessed by fluorescence polarization. These data provide further support for the concept that specific alterations in the cytoplasmic membrane of S. aureus strains are associated with tPMP-1 resistance in vitro.
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“The lipid profile of resting cells shows reorganisation after treatment with EO compounds, and many authors have described the bacterial fatty acid synthesis pathway as an optimal target of many antibacterial agents [73,74,75].”
From Effect of essential oils on pathogenic bacteria (2013) · cites this paper as [74]
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“An increase in the amount of SFAs in the membrane lipid bilayer results in a loss of membrane fluidity and a consequent increase in membrane rigidity [74].”
From Effect of essential oils on pathogenic bacteria (2013) · cites this paper as [74]
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Mechanisms of Antimicrobial Peptide Action and Resistance
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“Bayer et al. (2000) then compared parameters of membrane structure and function in genetically related S. aureus strains differing in tPMP-1 susceptibility or resistance.”
BackgroundResultEffect of essential oils on pathogenic bacteria
Nazzaro, F., Fratianni, F., De Martino, L., Coppola, R., & De Feo, V. (2013) · Pharmaceuticals · doi:10.3390/ph6121451 · Cited by 2,186
“An increase in the amount of SFAs in the membrane lipid bilayer results in a loss of membrane fluidity and a consequent increase in membrane rigidity [74].”
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Foster, T. J. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1289 · Cited by 1,214
Mechanisms and consequences of bacterial resistance to antimicrobial peptides
Andersson, D. I., Hughes, D., & Kubicek-Sutherland, J. Z. (2016) · Drug Resistance Updates · doi:10.1016/j.drup.2016.04.002 · Cited by 718
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BackgroundMembrane toxicity of antimicrobial compounds from essential oils
Di Pasqua, R., Betts, G., Hoskins, N., Edwards, M., Ercolini, D., & Mauriello, G. (2007) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0636465 · Cited by 648
Metadata
- Authors
- Bayer, A. S., Prasad, R., Chandra, J., Koul, A., Smriti, M., Varma, A., Skurray, R. A., Firth, N., Brown, M. H., Koo, S.-P., & Yeaman, M. R.
- Affiliations
- University of California, Los Angeles (US)
- Jawaharlal Nehru University (IN)
- The University of Sydney (AU)
- ORCID
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2000-06
- Volume
- 68
- Issue
- 6
- Pages
- 3548-3553
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC97641
- OpenAlex
- W2156172406
- Cited by
- 150
- References
- 52
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 6 · 2013: 9 · 2012: 14
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 39108, AI-39001, R01AI039108, R29AI039001, R01AI039001)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Staphylococcus aureus, antimicrobial resistance, membrane lipid composition, endocarditis, cationic antimicrobial peptides, multiresistance plasmid
- MeSH terms
- Amino Acids, Anti-Bacterial Agents, beta-Thromboglobulin, Biological Transport, Blood Proteins, Cell Membrane, DNA Transposable Elements, Drug Resistance, Microbial, Fatty Acids, Membrane Fluidity, Phenotype, Phospholipids, Species Specificity, Staphylococcus aureus, Mutagenesis, Insertional, Chemokines
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