Abstract
A common feature of cationic peptides is that their site of action is at the membrane due to channel formation, and that they tend to possess strong selectivity towards then target membrane. For example, although moth cecropin and bee melittin are members of the same family of peptides that adopt amphipathic α-helical structures, the cecropins are strongly antibacterial and demonstrate minimal eukaryotic selectivity (i.e., toxicity), whereas melittin is a weak antibacterial compound but a potent toxin. Whereas the basis for selectivity is not completely understood, it has been shown to be due to the size of the transmembrane electrical potential gradient (up to −140 mV in bacterial cytoplasmic membranes compared with about −20 mV or less in eukaryotic membranes) and the lipid composition (bacterial membranes contain a large number of anionic lipids such as phosphatidyl glycerol and cardiolipin and lack cholesterol in their membranes). Gram-negative bacteria have an additional, outer membrane, and our data suggests that a further level of selectivity is expressed there in that there are Gram-positive bacteria-selective peptides that interact poorly with the outer membrane but (presumably) well with cytoplasmic membranes, whereas we have identified peptides that interact with the outer membrane, but are not bactericidal and thus do not interact with cytoplasmic membranes.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Sawyer, J. G., Martin, N. L., and Hancock, R. E. W. (1988) Interaction of macrophage cationic proteins with the outer membrane of Pseudomonas aeruginosa. Infec. Immun. 56, 693–698.
Piers, K. L. and Hancock, R. E. W. (1994) The interaction of a recombinant cecropin/melittin hybrid peptide with the outer membrane of Pseudomonas aeruginosa. Molec. Microbiol. 12, 951–958.
Hancock, R. E. W. (1981) Ammoglycoside uptake and mode of action—with special reference to streptomycin and gentamicin. II. Effects of aminoglycosides on cells. Antimicrob. Chemother. 8, 429–445.
Hancock, R. E. W. (1991) Bacterial outer membranes evolving concepts. ASM News 57, 175–182.
Moore, R. A., Bates, N. C., and Hancock, R. E. W. (1986) Interaction of poly-cationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin. Antimicrob. Agents Chemother. 29, 496–500.
Hancock, R. E. W. and Wong, P. G. W. (1984) Compounds which increase the permeability of the Pseudomonas aeruginosa outer membrane. Antimicrob. Agents Chemother. 26, 48–52.
Loh, B., Grant, C., and Hancock, R. E. W. (1984) Use of the fluorescent probe 1-N-phenylnaphthylamine to study the interactions of aminoglycoside antibiotics with the outer membrane of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 26, 546–551.
Darveau, R. and Hancock, R. E. W. (1983) Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains. J. Bacteriol. 155, 831–838.
Vaara, M. (1992) Agents that increase the permeability of the outer membrane. Microbiol Rev. 56, 395–411.
Piers, K. L., Brown, M. H., and Hancock, R. E. W. (1994) Improvement of outer membrane-permeabilizing and lipopolysaccharide-binding activities of an antimicrobial cationic peptide by C-terminal modification. Antimicrob. Agents Chemother. 38, 2311–2316.
Matsuzaki, K., Harada M., Funakoshi, S., Fujii, N., and Miyajima, K. (1991) Physiochemical determinants for the interactions of magainins 1 and 2 with acidic lipid bilayers.Biochem Biophys Acta 1063, 162–170.
Sekharam, K. M., Bradrick, T. D., and Georghiou, S. (1991) Kinetics of melittin binding to phospholipid small unilamellar vesicles. Biochem Biophys Acta 1063, 171–174.
Vogel, H. and Jahnig, F. (1986) The structure of melittin in membranes. Biophys J. 50, 573–582.
Bechinger, B., Zasloff, M., and Opella, S. J. (1992) Structure and interactions of magainin antibiotic peptides in lipid bilayers: a solid-state nuclear magnetic resonance investigation. Biophys J. 62, 12–14.
Williams, R. W., Starman, R., Taylor, K. M. P., Gable, K., Beeler, T., Zasloff, M., and Covell, D. (1990) Raman spectroscopy of synthetic antimicrobial frog peptides magainin 2a and PGLa. Biochemistry 29, 4490–4496.
Sipos, D., Andersson, M/, and Ehrenberg, A. (1992) The structure of the mammalian antibacterial peptide cecropin PI in solution, determined by proton-NMR. Eur. J. Biochem. 209, 163–169.
Andreu, D., Ubach, J., Boman, A., Wahlur, B., Wade, D., Merrifield, R. B., and Boman, H. G. (1992) Shortened cecropin A-melittin hybrids. Significant size reductions retains potent antibiotic activity. FEBS Letts. 296, 190–194.
Agawa, Y., Lee, S., Ono, S., Aoyagi, H., Ohno, M., Tamguchi, T., Anzai, K., and Kirino, Y. (1991) Interaction with phospholipid bilayers, ion channel formation, and antimicrobial activity of basic amphiphilic alpha-helical model peptides of various chain lengths. J. Biol. Chem. 266, 20,218–20,222.
Christensen, B., Fink, J., Merrifield, R. B., and Mauzerall, D. (1988) Channel forming properties of cecropins and related model compounds incorporated into planar lipid membranes. PNAS. 85, 5072–5076.
Kagan, B. L., Selsted, M. E., Ganz, T., and Lehrer, R. I. (1990) Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. PNAS 87, 210–214.
Hanke, W., Methfessel, C., Wilmsen, H. U., Katz, E., Jung, G., and Bohem, G. (1983) Melittin and a chemically modified trichotoxin form alamethicin-type multistate pores. Biochem. Biophys. Acta 727, 108–114.
Kordel, M., Benz, R., and Sahl, H. G. (1988) Mode of action of the staphylococcin like peptide Pep5 voltage dependent depolarization of bacterial and artificial membranes. J. Bacteriol. 170, 84–88.
Cociancich, S., Ghazi, A., Hetru, C., Hoffman, J. A., and Letellier, L. J. (1993) Insect defensin, an inducible antibacterial peptide, forms voltage-dependent channels in Micrococcus luteus. Biol. Chem. 268, 19,239–19,245.
Pouny, Y., Rapaport, D., Mor, A., Nicolas, P., and Shai, Y. (1992) Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes. Biochemistry 31, 12,416–12,423.
Gazit, E., Boman, A., Boman, H. G., and Shai, Y. (1995) Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles. Biochemistry 34, 11,479–11,488.
Schindler, P. R. G. and Tueber, M. (1975) Action of Polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella typhimurium and Escherichia coli B. Antimicrob. Agents Chem. 8, 95–104.
Bader, J. and Teuber, M. (1973) Binding to the 0-antigenic lipopolysaccharide of Salmonella typhimurium. Z. Naturforsch. 28c, 422–430.
Kelly, N. M., Young, Y., and Cross, A. S. (1991) Differential induction of tumor necrosis factor by bacteria expressing rough and smooth lipopolysaccharide phenotypes. Infect. Immun. 59, 4491–4496.
Amsterdam, D. (1991) Antimicrobial combinations, in Antibiotics in Laboratory Medicine. (Lorian, V., ed.) Williams and Wilkins, Baltimore, pp 432–492.
Peterson, A. A., Hancock, R. E. W., and McGroarty, J. (1985) Binding of polycationic antibiotics and polyamines to lipopolysaccharides of Pseudomonas aeruginosa. J. Bacteriol. 164, 1256–1261.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Humana Press Inc.
About this protocol
Cite this protocol
Fidai, S., Farmer, S.W., Hancock, R.E.W. (1997). Interaction of Cationic Peptides with Bacterial Membranes. In: Shafer, W.M. (eds) Antibacterial Peptide Protocols. Methods In Molecular Biology™, vol 78. Humana Press. https://doi.org/10.1385/0-89603-408-9:187
Download citation
DOI: https://doi.org/10.1385/0-89603-408-9:187
Publisher Name: Humana Press
Print ISBN: 978-0-89603-408-2
Online ISBN: 978-1-59259-564-8
eBook Packages: Springer Protocols