Cited by 1,879Bacterial Genetics and BiotechnologyAntimicrobial Peptides and ActivitiesAntimicrobial agents and applications

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Agents that increase the permeability of the outer membrane

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Vaara, M·1992·Microbiological Reviews

DOI 10.1128/mr.56.3.395-411.1992PMC PMC372877

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Abstract

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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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)
DOI: 10.1128/mr.56.3.395-411.1992
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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