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Agents that increase the permeability of the outer membrane
Open accessAbstract
The outer membrane of gram-negative bacteria provides the cell with an effective permeability barrier against external noxious agents, including antibiotics, but is itself a target for antibacterial agents such as polycations and chelators. Both groups of agents weaken the molecular interactions of the lipopolysaccharide constituent of the outer membrane. Various polycations are able, at least under certain conditions, to bind to the anionic sites of lipopolysaccharide. Many of these disorganize and cross the outer membrane and render it permeable to drugs which permeate the intact membrane very poorly. These polycations include polymyxins and their derivatives, protamine, polymers of basic amino acids, compound 48/80, insect cecropins, reptilian magainins, various cationic leukocyte peptides (defensins, bactenecins, bactericidal/permeability-increasing protein, and others), aminoglycosides, and many more. However, the cationic character is not the sole determinant required for the permeabilizing activity, and therefore some of the agents are much more effective permeabilizers than others. They are useful tools in studies in which the poor permeability of the outer membrane poses problems. Some of them undoubtedly have a role as natural antibiotic substances, and they or their derivatives might have some potential as pharmaceutical agents in antibacterial therapy as well. Also, chelators (such as EDTA, nitrilotriacetic acid, and sodium hexametaphosphate), which disintegrate the outer membrane by removing Mg2+ and Ca2+, are effective and valuable permeabilizers.
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“However, thymol and carvacrol do not directly act as OM permeabilising agents (unlike EDTA or polyethylenimine, which disintegrate the OM at sub-lethal concentrations) [9,14].”
From Effect of essential oils on pathogenic bacteria (2013) · cites this paper as [9]
In the citing paper
“The presence of an outer membrane in Gram-negative bacteria acts as a powerful barrier, restricting the diffusion of compounds through its lipopolysaccharide layer [56].”
From Comparison of Techniques and Solvents on the Antimicrobial and Antioxidant Potential of Extracts from Acacia dealbata and Olea europaea (2020) · cites this paper as [56]
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Correa, M. D. S., Bombardelli, M. C. M., Fontana, P. D., Bovo, F., Messias-Reason, I., Maurer, J. B. B., & Corazza, M. L. (2016) · The Journal of Supercritical Fluids · doi:10.1016/j.supflu.2016.12.004 · Cited by 24
Elbali, W., Djouahri, A., Djerrad, Z., Saka, B., Aberrane, S., Sabaou, N., Baâliouamer, A., & Boudarene, L. (2018) · Journal of Essential Oil Research · doi:10.1080/10412905.2018.1493405 · Cited by 24
Lipid A--Target for Antibacterial Drugs
Vaara, M. (1996) · Science · doi:10.1126/science.274.5289.939 · Cited by 24
Self-citationChemical Structure of the Lipid A Component of Lipopolysaccharides of the Genus Pectinatus
Helander, I. M., Kilpeläinen, I., Vaara, M., Moran, A. P., Lindner, B., & Seydel, U. (1994) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1994.tb19995.x · Cited by 24
Self-citationVuorio, R., & Vaara, M. (1992) · Journal of Bacteriology · doi:10.1128/jb.174.22.7090-7097.1992 · Cited by 24
Self-citationSamantaray, P. K., Baloda, S., Madras, G., & Bose, S. (2019) · ACS Sustainable Chemistry & Engineering · doi:10.1021/acssuschemeng.9b02916 · Cited by 23
Djague, F., Lunga, P. K., Toghueo, R. M. K., Melogmo, Y. K. D., & Boyom, F. F. (2020) · PLoS ONE · doi:10.1371/journal.pone.0237076 · Cited by 23
Zhou, C., Wang, Q., Jin, L., Wang, R., Yin, Y., Sun, S., Zhang, J., & Wang, H. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.533209 · Cited by 25
Metadata
- Authors
- Vaara, M.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Vaara, M
- ORCID
- Vaara, M
- Venue
- Microbiological Reviews
- Publisher
- American Society for Microbiology
- Published
- 1992-09
- Volume
- 56
- Issue
- 3
- Pages
- 395-411
- ISSN
- 0146-0749 (ISSN-L)
- PMC
- PMC372877
- OpenAlex
- W1895129045
- Cited by
- 1,879
- References
- 229
- Citations by year
- 2026: 33 · 2025: 73 · 2024: 48 · 2023: 70 · 2022: 89 · 2021: 104 · 2020: 75 · 2019: 99 · 2018: 75 · 2017: 91 · 2016: 91 · 2015: 72 · 2014: 77 · 2013: 79 · 2012: 77
- FWCI
- 16.64
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Microbiological Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antimicrobial agents and applications
- Keywords
- outer membrane permeabilization, Gram-negative bacterial outer membrane, lipopolysaccharide, cationic polymers, cationic antimicrobial peptides, polymyxins, magainin, cecropin, defensins, bactenecin, bactericidal/permeability-increasing protein, aminoglycosides, chelating agents, EDTA, antibiotic resistance, antibacterial agents
- MeSH terms
- Amino Acid Sequence, Anti-Bacterial Agents, Bacterial Outer Membrane Proteins, Cell Membrane Permeability, Drug Resistance, Microbial, Gram-Negative Bacteria, Lipopolysaccharides, Molecular Sequence Data
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