Modulation of the Hydrophobic Domain of Polymyxin B Nonapeptide: Effect on Outer-Membrane Permeabilization and Lipopolysaccharide Neutralization

Tsubery, Haim; Ofek, Itzhak; Cohen, SB; Eisenstein, Miriam; Fridkin, Mati

doi:10.1124/mol.62.5.1036

Cited by 63 publications

(60 citation statements)

References 29 publications

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“…Many excellent reports that provide insight into the importance of peptide sequences and structures in antimicrobial activity have been published (for a review see reference 23). In several cases, it has been demonstrated that antimicrobial activity does not correlate with binding affinity (25,27). When binding affinity and antimicrobial activity are not interrelated, the peptide often binds to the membrane with high affinity but lacks the ability to exhibit antimicrobial activity.…”

Section: Discussionmentioning

confidence: 99%

“…More likely, differences in cell surface chemistry between the two strains of E. coli were responsible for the specific binding. Studies of the surface localization of outer membrane constituents indicate that lipopolysaccharide is the most likely site of antimicrobial peptide binding (17,20,27). Lipopolysaccharide is an amphipathic molecule with a hydrophobic, well-conserved lipid A region and a highly variable hydrophilic region.…”

Section: Discussionmentioning

confidence: 99%

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Immobilization ofEscherichia coliCells by Use of the Antimicrobial Peptide Cecropin P1

Gregory

Mello²

2005

Appl Environ Microbiol

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An immobilization scheme for bacterial cells is described, in which the antimicrobial peptide cecropin P1 was used to trap Escherichia coli K-12 and O157:H7 cells on microtiter plate well surfaces. Cecropin P1 was covalently attached to the well surfaces, and E. coli cells were allowed to bind to the peptide-coated surface. The immobilized cells were detected colorimetrically with an anti-E. coli antibody-horseradish peroxidase conjugate. Binding curves were obtained in which the signal intensities were dependent upon the cell concentration and upon the amount of peptide attached to the well surface. After normalization for the amount of peptide coupled to the surface and the relative binding affinity of the antibody for each strain, the binding data were compared, which indicated that there was a strong preference for E. coli O157:H7 over E. coli K-12. The cells could be immobilized reproducibly at pH values ranging from 5 to 10 and at ionic strengths up to 0.50 M.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immobilization ofEscherichia coliCells by Use of the Antimicrobial Peptide Cecropin P1

Gregory

Mello²

2005

Appl Environ Microbiol

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“…Recently, total or semisynthesis or modifications of polymyxins was performed chemically or enzymatically, and the resulting products were effectively used for structure-function study (6,20,36,45,50,52). There is a limitation to obtaining diverse derivatives by using chemical or enzymatic approaches, however, and this limitation is related to the structural complexity of polymyxin.…”

mentioning

confidence: 99%

Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis

Choi

Park

Kim³

et al. 2009

J Bacteriol

142

133

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Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the treatment of multidrug-resistant gram-negative pathogenic bacteria. Lack of information on the biosynthetic genes of polymyxin, however, has limited the study of structure-function relationships and the development of improved polymyxins. During whole genome sequencing of Paenibacillus polymyxa E681, a plant growth-promoting rhizobacterium, we identified a gene cluster encoding polymyxin synthetase. Here, we report the complete sequence of the gene cluster and its function in polymyxin biosynthesis. The gene cluster spanning the 40.6-kb region consists of five open reading frames, designated pmxA, pmxB, pmxC, pmxD, and pmxE. The pmxC and pmxD genes are similar to genes that encode transport proteins, while pmxA, pmxB, and pmxE encode polymyxin synthetases. The insertional disruption of pmxE led to a loss of the ability to produce polymyxin. Introduction of the pmx gene cluster into the amyE locus of the Bacillus subtilis chromosome resulted in the production of polymyxin in the presence of extracellularly added L-2,4-diaminobutyric acid. Taken together, our findings demonstrate that the pmx gene cluster is responsible for polymyxin biosynthesis.

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“…Most of the iron-independent antibacterial activity of Lf is concentrated into a cluster of positively charged residues near the N-terminus of the Lfs from many mammalian species [40][41][42][43]. This positive cluster binds to the lipid A part of LPS molecules present on the outer membrane of clinically relevant bacterial species [44,45], acting therefore in a way similar to that of a number of polycationic compounds, such as polymyxin B nonapeptide [46]. In addition, following the observation that LPS release induced by Lf is neutralised by high calcium concentration in the medium, Ellison et al [47] hypothesised that Lf could be broadly active as a calcium chelator such as EDTA, which is known to induce LPS release [48].…”

Section: Bactericidal Activity Not Related To Iron Withholdingmentioning

confidence: 99%

Lactoferrin

Valenti

Antonini

2005

Cell. Mol. Life Sci.

416

165

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The first function attributed to lactoferrin (Lf), an iron binding protein belonging to the non-immune natural defences, was antimicrobial activity that depended on its capacity to sequester iron. Iron-independent microbicidal activities, requiring direct interaction between this cationic protein and microbial surface components, were later demonstrated. Many other anti-microbial and anti-viral functions have since been ascribed to Lf. In mucosal secretions, iron and Lf modulate the motility and aggregation of pathogenic bacteria. Lf inhibits bacterial adhesion on abiotic surfaces through ionic binding to biomaterials, or specific binding to bacterial structures or both. Lf inhibition of bacterial adhesion to host cells requires Lf binding to bacteria and/or host cells. Lf hinders microbial internalization by binding to both glycosaminoglycans and bacterial proteins which can be degraded by Lf-mediated proteolysis. Moreover, Lf internalisation and localisation to the host cell nuclei could modulate bacterial entry into cells through gene regulation. Finally, the capability of Lf to exert antiviral activity, through its binding to host cells and/or viral particles, strengthens the idea that it is an important brick in the mucosal wall, effective against both microbial and viral attacks.

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Modulation of the Hydrophobic Domain of Polymyxin B Nonapeptide: Effect on Outer-Membrane Permeabilization and Lipopolysaccharide Neutralization

Cited by 63 publications

References 29 publications

Immobilization ofEscherichia coliCells by Use of the Antimicrobial Peptide Cecropin P1

Immobilization ofEscherichia coliCells by Use of the Antimicrobial Peptide Cecropin P1

Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis

Lactoferrin

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