Cystic fibrosis (CF) is a severe and diffuse recessive genetic disease due to defects of the CF Transmembrane conductance Regulator (CFTR) gene. CF affects several organs, with the chronic pulmonary disease being the major cause of reduction of the quality and expectancy of life. The hallmark of CF lung disease is chronic infection generally sustained by the gram-negative bacterium Pseudomonas aeruginosa and excessive lung inflammation with a huge infiltrate of neutrophils in the bronchial lumen, mainly due to the release of the chemokine interleukin IL-8. [1] The identification of innovative drugs exhibiting strong antibacterial activity and thereby able to reduce the excessive lung inflammation in CF patients, is considered a promising therapeutic target to prevent the progressive lung tissue deterioration. The aim of the present study is to determine the activity of the peptide TB_KKG6A on P.aeruginosa growth and downstream biological effects on the cystic fibrosis IB3-1 cell line and characterize the interaction of the peptide with the P.aeruginosa LPS. TB_KKG6A is a recently developed analogue of temporin B (TB), active against Gram positive and Gram negative bacteria at low concentration.[2] We investigated the antimicrobial activity of TB_KKG6A against P.aeruginosa PAO1 strain and also evaluated the amount of IL-8 produced in IB3-1 cells in different experimental conditions. Experiments were carried out in parallel on TB, TB_G6A (a different TB analogue) and gentamicin, which is the gold standard in the treatment of infections in CF affected patients. Interactions of TB_KKG6A with bacterial LPS were investigated by Circular Dichroism and by fluorescence to gain information on the peptide-LPS binding. References 1. T.L. Bonfield, J.R. Panuska, M.W. Konstan, K.A. Hilliard, J.B. Hilliard, H. Ghnaim, M. Berger American Journal of Respiratory and Critical Care Medicine (1995), 152, 2111. 2. Avitabile C., Netti F., Orefice G., Palmieri M., Nocerino N., Malgieri G., D’Andrea L.D., Capparelli R., Fattorusso R., Romanelli A. et al Biochimica et biophysica acta (2013), 1830, 3767.

Antibacterial and anti-inflammatory activity of a Temporin B peptide analogue on an in vitro model of cystic fibrosis / C., Avitabile; V., Bezzerri; G., Cabrini; C., De Checchi; I., Lampronti; M., Borgatti; R., Gambari; Romanelli, Alessandra. - (2013). (Intervento presentato al convegno Convegno Nazionale della Divisione di Chimica dei Sistemi Biologici, Bertinoro, tenutosi a Bertinoro (FC) nel 19-20 settembre 2013).

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

ROMANELLI, ALESSANDRA
2013

Abstract

Cystic fibrosis (CF) is a severe and diffuse recessive genetic disease due to defects of the CF Transmembrane conductance Regulator (CFTR) gene. CF affects several organs, with the chronic pulmonary disease being the major cause of reduction of the quality and expectancy of life. The hallmark of CF lung disease is chronic infection generally sustained by the gram-negative bacterium Pseudomonas aeruginosa and excessive lung inflammation with a huge infiltrate of neutrophils in the bronchial lumen, mainly due to the release of the chemokine interleukin IL-8. [1] The identification of innovative drugs exhibiting strong antibacterial activity and thereby able to reduce the excessive lung inflammation in CF patients, is considered a promising therapeutic target to prevent the progressive lung tissue deterioration. The aim of the present study is to determine the activity of the peptide TB_KKG6A on P.aeruginosa growth and downstream biological effects on the cystic fibrosis IB3-1 cell line and characterize the interaction of the peptide with the P.aeruginosa LPS. TB_KKG6A is a recently developed analogue of temporin B (TB), active against Gram positive and Gram negative bacteria at low concentration.[2] We investigated the antimicrobial activity of TB_KKG6A against P.aeruginosa PAO1 strain and also evaluated the amount of IL-8 produced in IB3-1 cells in different experimental conditions. Experiments were carried out in parallel on TB, TB_G6A (a different TB analogue) and gentamicin, which is the gold standard in the treatment of infections in CF affected patients. Interactions of TB_KKG6A with bacterial LPS were investigated by Circular Dichroism and by fluorescence to gain information on the peptide-LPS binding. References 1. T.L. Bonfield, J.R. Panuska, M.W. Konstan, K.A. Hilliard, J.B. Hilliard, H. Ghnaim, M. Berger American Journal of Respiratory and Critical Care Medicine (1995), 152, 2111. 2. Avitabile C., Netti F., Orefice G., Palmieri M., Nocerino N., Malgieri G., D’Andrea L.D., Capparelli R., Fattorusso R., Romanelli A. et al Biochimica et biophysica acta (2013), 1830, 3767.
2013
Antibacterial and anti-inflammatory activity of a Temporin B peptide analogue on an in vitro model of cystic fibrosis / C., Avitabile; V., Bezzerri; G., Cabrini; C., De Checchi; I., Lampronti; M., Borgatti; R., Gambari; Romanelli, Alessandra. - (2013). (Intervento presentato al convegno Convegno Nazionale della Divisione di Chimica dei Sistemi Biologici, Bertinoro, tenutosi a Bertinoro (FC) nel 19-20 settembre 2013).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/581656
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