Dataset Information

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.

ABSTRACT: Eradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and/or biofilm forms of Pseudomonas aeruginosa strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.

SUBMITTER: Pulido D

PROVIDER: S-EPMC5038260 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.

Pulido David D Prats-Ejarque Guillem G Villalba Clara C Albacar Marcel M González-López Juan J JJ Torrent Marc M Moussaoui Mohammed M Boix Ester E

Antimicrobial agents and chemotherapy 20160923 10

Eradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutin ...[more]

PMID: 27527084

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Project description:Microbial biofilms have great negative impacts on the world's economy and pose serious problems to industry, public health and medicine. The interest in the development of new approaches for the prevention and treatment of bacterial adhesion and biofilm formation has increased. Since, bacterial pathogens living in biofilm induce persistent chronic infections due to the resistance to antibiotics and host immune system. A viable approach should target adhesive properties without affecting bacterial vitality in order to avoid the appearance of resistant mutants. Many bacteria secrete anti-biofilm molecules that function in regulating biofilm architecture or mediating the release of cells from it during the dispersal stage of biofilm life cycle. Cold-adapted marine bacteria represent an untapped reservoir of biodiversity able to synthesize a broad range of bioactive compounds, including anti-biofilm molecules. The anti-biofilm activity of cell-free supernatants derived from sessile and planktonic cultures of cold-adapted bacteria belonging to Pseudoalteromonas, Psychrobacter, and Psychromonas species were tested against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa strains. Reported results demonstrate that we have selected supernatants, from cold-adapted marine bacteria, containing non-biocidal agents able to destabilize biofilm matrix of all tested pathogens without killing cells. A preliminary physico-chemical characterization of supernatants was also performed, and these analyses highlighted the presence of molecules of different nature that act by inhibiting biofilm formation. Some of them are also able to impair the initial attachment of the bacterial cells to the surface, thus likely containing molecules acting as anti-biofilm surfactant molecules. The described ability of cold-adapted bacteria to produce effective anti-biofilm molecules paves the way to further characterization of the most promising molecules and to test their use in combination with conventional antibiotics.

Project description:Biofilms are microbial communities encased in a protective matrix composed of exopolymeric substances including exopolysaccharides, proteins, lipids, and extracellular DNA. Biofilms cause undesirable effects such as biofouling, equipment damage, prostheses colonization, and disease. Biofilms are also more resilient than free-living cells to regular decontamination methods and therefore, alternative methods are needed to eradicate them. The use of non-thermal atmospheric pressure plasmas is a good alternative as plasmas contain reactive species, free radicals, and UV photons well-known for their decontamination potential against free microorganisms. Pseudomonas aeruginosa biofilms colonize catheters, indwelling devices, and prostheses. Plasma effects on cell viability have been previously documented for P. aeruginosa biofilms. Nonetheless, the effect of plasma on the biofilm matrix has received less attention and there is little evidence regarding the changes the matrix undergoes. The aim of this work was to study the effect plasma exerts mostly on the P. aeruginosa biofilm matrix and to expand the existing knowledge about its effect on sessile cells in order to achieve a better understanding of the mechanism/s underlying plasma-mediated biofilm inactivation. We report a reduction in the amount of the biofilm matrix, the loss of its tridimensional structure, and morphological changes in sessile cells at long exposure times. We show chemical and structural changes on the biofilm matrix (mostly on carbohydrates and eDNA) and cells (mostly on proteins and lipids) that are more profound with longer plasma exposure times. We also demonstrate the presence of lipid oxidation products confirming cell membrane lipid peroxidation as plasma exposure time increases. To our knowledge this is the first report providing detailed evidence of the variety of chemical and structural changes that occur mostly on the biofilm matrix and sessile cells as a consequence of the plasma treatment. Based on our results, we propose a comprehensive model explaining plasma-mediated biofilm inactivation.

Dataset Information

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.

Publications

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.

Similar Datasets

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