Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes?

Papo, Niv; Shai, Yechiel

doi:10.1016/j.peptides.2003.09.013

Cited by 278 publications

(244 citation statements)

References 99 publications

Supporting

Mentioning

233

Contrasting

Unclassified

Order By: Relevance

“…Studies on their plausible mode of action support a membranolytic or detergent-like effect [probably via the carpet mechanism (10)] that, similar to many membrane-active AMPs, should make it difficult for the microorganisms to develop resistance. The detergent-like properties of AMPs have been discussed (31)(32)(33)(34). Furthermore, the incorporation of D amino acids should give these lipopeptides several advantages compared with their all L amino acid parental lipopeptides, such as controlled enzymatic degradation, which has been recently shown for 15-mer diastereomeric antibacterial peptides (35).…”

Section: Discussionmentioning

confidence: 99%

“…SUVs were prepared by dissolving dry lipids in chloroform͞MeOH (2:1, vol͞vol), evaporating the solvent under a stream of nitrogen, lyophilizing overnight, resuspending in buffer (10 mg͞ml), vortex mixing, and sonicating. Lipid films were prepared from PC͞PE͞PI͞ergosterol (5:4:1:2, wt͞wt͞wt͞wt), PE͞PG (7:3, wt͞wt), and PC͞cholesterol (10:1, wt͞wt), which mimic the outer leaflets of the plasma membranes of C. albicans (32), E. coli (33), and hRBCs (34), respectively.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Ultrashort antibacterial and antifungal lipopeptides

Makovitzki

Avrahami

Shai

2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

417

384

View full text Add to dashboard Cite

Host-defense cationic antimicrobial peptides (Ϸ12-50 aa long) play an essential protective role in the innate immune system of all organisms. Lipopeptides, however, are produced only in bacteria and fungi during cultivation, and they are composed of specific lipophilic moieties attached to anionic peptides (six to seven amino acids). Here we report the following. (i) The attachment of an aliphatic chain to otherwise inert, cationic D,L tetrapeptides endows them with potent activity against various microorganisms including antibiotic resistance strains. (ii) Cell specificity is determined by the sequence of the short peptidic chain and the length of the aliphatic moiety. (iii) Despite the fact that the peptidic chains are very short, their mode of action involves permeation and disintegration of membranes, similar to that of many long antimicrobial peptides. Besides adding important information on the parameters necessary for host-defense lipopeptides to kill microorganisms, the simple composition of these lipopeptides and their diverse specificities should make them economically available, innate immunity-mimicking antimicrobial and antifungal compounds for various applications.antimicrobial peptides ͉ innate immunity ͉ peptide-membrane interaction ͉ carpet model ͉ lytic peptides

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Ultrashort antibacterial and antifungal lipopeptides

Makovitzki

Avrahami

Shai

2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

417

384

View full text Add to dashboard Cite

show abstract

“…The hydrophobic-hydrophilic balance is a crucial factor for lipid-peptide interactions (37) and is related to their antibacterial activity (54,55). The main target of antimicrobial peptides is the bacteria inner membrane, with a net negative charge (25,56,57). The interaction of the protein with the membrane would involve both hydrophobic interactions with the lipid acyl chain and electrostatic interactions between the positive residues and anionic phospholipid head groups (58,59).…”

Section: Discussionmentioning

confidence: 99%

“…While the insertion of some peptides can be spontaneously driven mainly by the hydrophobic effect, the electrostatic attractions are needed for the peptides that require a surface association step before membrane insertion (68,69). According to the "carpet model", the protein would bind to the membrane surface until a threshold concentration is reached and then would be able to permeate it in a detergent-like manner (57). In fact, we do observe for ECP the onset of a liposome aggregation activity, from a threshold concentration, in the range of 100-200 nM ( Figure 5), depending upon the vesicle composition.…”

Section: Discussionmentioning

confidence: 99%

Topography Studies on the Membrane Interaction Mechanism of the Eosinophil Cationic Protein

et al. 2006

View full text Add to dashboard Cite

The eosinophil cationic protein (ECP) is an antipathogen protein involved in the host defense system. ECP displays bactericidal and membrane lytic capacities [Carreras et al. (2003) Biochemistry 42, 6636-6644]. We have now characterized in detail the protein-membrane interaction process. All observed fluorescent parameters of the wild type and single-tryptophan-containing mutants, as well as the results of decomposition analysis of protein fluorescence, suggest that W10 and W35 belong to two distinct spectral classes I and III, respectively. Tryptophan residues were classified and assigned to distinct structural classes using statistical approaches based on the analysis of tryptophan microenvironment structural properties. W10 belongs to class I and is buried in a relative nonpolar, nonflexible protein environment, while W35 (class III) is fully exposed to free water molecules. Tryptophan solvent exposure and the depth of the protein insertion in the lipid bilayer were monitored by the degree of protein fluorescence quenching by KI and brominated phospholipids, respectively. Results indicate that W35 partially inserts into the lipid bilayer, whereas W10 does not. Further analysis by electron microscopy and dynamic light scattering indicates that ECP can destabilize and trigger lipid vesicle aggregation at a nanomolar concentration range, corresponding to about 1:1000 protein/lipid ratio. No significant leakage of the vesicle aqueous content takes place below that protein concentration threshold. The data are consistent with a membrane destabilization "carpet-like" mechanism.

show abstract

“…Two mechanisms have been proposed to explain the mode of action of antibacterial peptides: 1) permeabilization of the bacterial cytoplasmic membrane and 2) penetration of the cell membrane followed by interaction with intracellular targets (5,6). In the case of the former, membrane-targeting antibacterial peptides aggregate on the surface of bacterial cells and then penetrate into the lipid membrane to form transmembrane channels or pores (7,8). In the case of latter, the peptides penetrate all the way through the membrane and then inhibit various intracellular functions, including cell wall, nucleic acid and protein synthesis (9).…”

Section: Introductionmentioning

confidence: 99%

Different modes of antibiotic action of homodimeric and monomeric bactenecin, a cathelicidin-derived antibacterial peptide

Lee

Yang²,

Kim³

et al. 2009

BMB Reports

View full text Add to dashboard Cite

The bactenecin is an antibacterial peptide with an intramolecular disulfide bond. We recently found that homodimeric bactenecin exhibits more potent antibacterial activity than the monomeric form and retains its activity at physiological conditions. Here we assess the difference in the modes of antibiotic action of homodimeric and monomeric bactenecins. Both monomeric and dimeric bactenecins almost completely killed both Staphylococcus aureus and E. coli within 10-30 min at concentrations of 8-16 μM. However, exposure to liposomes elicited an increase in the fluorescence quantum yield from a tryptophan-containing monomeric analog, while the homodimeric analog showed a significant reduction in fluorescence intensity. Moreover, unlike the monomer, the homodimer displayed apparent membrane-lytic activity enabling release of various sized dyes from liposomes, and rapidly and fully depolarized the S. aureus membrane. Together, our results suggest that homodimeric bactenecin forms pores in the bacterial membrane, while monomeric one penetrates through the membrane to target intracellular molecules/ organelles. [BMB reports 2009; 42(9): 586-592]

show abstract

Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes?

Cited by 278 publications

References 99 publications

Ultrashort antibacterial and antifungal lipopeptides

Ultrashort antibacterial and antifungal lipopeptides

Topography Studies on the Membrane Interaction Mechanism of the Eosinophil Cationic Protein

Different modes of antibiotic action of homodimeric and monomeric bactenecin, a cathelicidin-derived antibacterial peptide

Contact Info

Product

Resources

About