Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive since their activity can easily be tuned after small modification to their primary sequence. Structure-activity studies allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram positive and Gram negative bacteria. In this study we investigated the antimicrobial and anti-inflammatory activity of the peptide TB_KKG6A against Pseudomonas aeruginosa. Experiments aimed to evaluate the antimicrobial activity of TB_KKG6A were carried out in parallel also on temporin B, TB_G6A and gentamycin. Details on the interaction between TB_KKG6A and the P. aeruginosa LPS were obtained by CD and fluorescence studies. Interestingly TB_KKG6A was found active against P. aeruginosa at 10 µM concentration, unlike the other peptides which were found inactive. Interestingly we found that the peptide exhibit antimicrobial activity at low concentrations, being able to down-regulate the pro-inflammatory chemokines and cytokines IL-8, IL-1β, IL-6 and TNF-α produced downstream in infected human bronchial epithelial cells. The inhibitory effects of TB_KKG6A are detectable in IB3-1-infected cells in the protocol mimicking the pathological situation and based on pre-treatment of IB3-1 cells with the inhibitory peptide before infection. The effects of TB_KKG6A on IL-8 gene expression are of relevance in consideration of the key role of this protein in cystic fibrosis inflammatory process.

Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive because their activity can easily be tuned after small modification to their primary sequence. Structure-activity studies previously reported by us allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this paper, we investigated the antimicrobial and anti-inflammatory activity of the peptide TB_KKG6A against Pseudomonas aeruginosa. Interestingly, we found that the peptide exhibits antimicrobial activity at low concentrations, being able to downregulate the pro-inflammatory chemokines and cytokines interleukin (IL)-8, IL-1, IL-6 and tumor necrosis factor- produced downstream infected human bronchial epithelial cells. Experiments were carried out also with temporin B, which was found to show pro-inflammatory activity. Details on the interaction between TB_KKG6A and the P. aeruginosa LPS were obtained by circular dichroism and fluorescence studies. Copyright (c) 2014 European Peptide Society and John Wiley & Sons, Ltd.

Antibacterial and anti-inflammatory activity of a Temporin B peptide analogue on a in vitro model of cystic fibrosis.

LAMPRONTI, Ilaria;BORGATTI, Monica;MONTAGNER, Giulia;GAMBARI, Roberto;
2014

Abstract

Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive since their activity can easily be tuned after small modification to their primary sequence. Structure-activity studies allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram positive and Gram negative bacteria. In this study we investigated the antimicrobial and anti-inflammatory activity of the peptide TB_KKG6A against Pseudomonas aeruginosa. Experiments aimed to evaluate the antimicrobial activity of TB_KKG6A were carried out in parallel also on temporin B, TB_G6A and gentamycin. Details on the interaction between TB_KKG6A and the P. aeruginosa LPS were obtained by CD and fluorescence studies. Interestingly TB_KKG6A was found active against P. aeruginosa at 10 µM concentration, unlike the other peptides which were found inactive. Interestingly we found that the peptide exhibit antimicrobial activity at low concentrations, being able to down-regulate the pro-inflammatory chemokines and cytokines IL-8, IL-1β, IL-6 and TNF-α produced downstream in infected human bronchial epithelial cells. The inhibitory effects of TB_KKG6A are detectable in IB3-1-infected cells in the protocol mimicking the pathological situation and based on pre-treatment of IB3-1 cells with the inhibitory peptide before infection. The effects of TB_KKG6A on IL-8 gene expression are of relevance in consideration of the key role of this protein in cystic fibrosis inflammatory process.
Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive because their activity can easily be tuned after small modification to their primary sequence. Structure-activity studies previously reported by us allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this paper, we investigated the antimicrobial and anti-inflammatory activity of the peptide TB_KKG6A against Pseudomonas aeruginosa. Interestingly, we found that the peptide exhibits antimicrobial activity at low concentrations, being able to downregulate the pro-inflammatory chemokines and cytokines interleukin (IL)-8, IL-1, IL-6 and tumor necrosis factor- produced downstream infected human bronchial epithelial cells. Experiments were carried out also with temporin B, which was found to show pro-inflammatory activity. Details on the interaction between TB_KKG6A and the P. aeruginosa LPS were obtained by circular dichroism and fluorescence studies. Copyright (c) 2014 European Peptide Society and John Wiley & Sons, Ltd.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2231412
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