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Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein lead to persistent lung bacterial infections, mainly due to Pseudomonas aeruginosa, causing loss of respiratory function and finally death of people affected by CF. Unfortunately, even in the era of CFTR modulat...

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Autores principales: Ferrera, Loretta, Cappiello, Floriana, Loffredo, Maria Rosa, Puglisi, Elena, Casciaro, Bruno, Botta, Bruno, Galietta, Luis J. V., Mori, Mattia, Mangoni, Maria Luisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752549/
https://www.ncbi.nlm.nih.gov/pubmed/34971429
http://dx.doi.org/10.1007/s00018-021-04030-2
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author Ferrera, Loretta
Cappiello, Floriana
Loffredo, Maria Rosa
Puglisi, Elena
Casciaro, Bruno
Botta, Bruno
Galietta, Luis J. V.
Mori, Mattia
Mangoni, Maria Luisa
author_facet Ferrera, Loretta
Cappiello, Floriana
Loffredo, Maria Rosa
Puglisi, Elena
Casciaro, Bruno
Botta, Bruno
Galietta, Luis J. V.
Mori, Mattia
Mangoni, Maria Luisa
author_sort Ferrera, Loretta
collection PubMed
description Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein lead to persistent lung bacterial infections, mainly due to Pseudomonas aeruginosa, causing loss of respiratory function and finally death of people affected by CF. Unfortunately, even in the era of CFTR modulation therapies, management of pulmonary infections in CF remains highly challenging especially for patients with advanced stages of lung disease. Recently, we identified antimicrobial peptides (AMPs), namely Esc peptides, with potent antipseudomonal activity. In this study, by means of electrophysiological techniques and computational studies we discovered their ability to increase the CFTR-controlled ion currents, by direct interaction with the F508del-CFTR mutant. Remarkably, this property was not explored previously with any AMPs or peptides in general. More interestingly, in contrast with clinically used CFTR modulators, Esc peptides would give particular benefit to CF patients by combining their capability to eradicate lung infections and to act as promoters of airway wound repair with their ability to ameliorate the activity of the channel with conductance defects. Overall, our findings not only highlighted Esc peptides as the first characterized AMPs with a novel property, that is the potentiator activity of CFTR, but also paved the avenue to investigate the functions of AMPs and/or other peptide molecules, for a new up-and-coming pharmacological approach to address CF lung disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-04030-2.
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spelling pubmed-87525492022-01-20 Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides Ferrera, Loretta Cappiello, Floriana Loffredo, Maria Rosa Puglisi, Elena Casciaro, Bruno Botta, Bruno Galietta, Luis J. V. Mori, Mattia Mangoni, Maria Luisa Cell Mol Life Sci Original Article Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein lead to persistent lung bacterial infections, mainly due to Pseudomonas aeruginosa, causing loss of respiratory function and finally death of people affected by CF. Unfortunately, even in the era of CFTR modulation therapies, management of pulmonary infections in CF remains highly challenging especially for patients with advanced stages of lung disease. Recently, we identified antimicrobial peptides (AMPs), namely Esc peptides, with potent antipseudomonal activity. In this study, by means of electrophysiological techniques and computational studies we discovered their ability to increase the CFTR-controlled ion currents, by direct interaction with the F508del-CFTR mutant. Remarkably, this property was not explored previously with any AMPs or peptides in general. More interestingly, in contrast with clinically used CFTR modulators, Esc peptides would give particular benefit to CF patients by combining their capability to eradicate lung infections and to act as promoters of airway wound repair with their ability to ameliorate the activity of the channel with conductance defects. Overall, our findings not only highlighted Esc peptides as the first characterized AMPs with a novel property, that is the potentiator activity of CFTR, but also paved the avenue to investigate the functions of AMPs and/or other peptide molecules, for a new up-and-coming pharmacological approach to address CF lung disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-04030-2. Springer International Publishing 2021-12-31 2022 /pmc/articles/PMC8752549/ /pubmed/34971429 http://dx.doi.org/10.1007/s00018-021-04030-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Ferrera, Loretta
Cappiello, Floriana
Loffredo, Maria Rosa
Puglisi, Elena
Casciaro, Bruno
Botta, Bruno
Galietta, Luis J. V.
Mori, Mattia
Mangoni, Maria Luisa
Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides
title Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides
title_full Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides
title_fullStr Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides
title_full_unstemmed Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides
title_short Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides
title_sort esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752549/
https://www.ncbi.nlm.nih.gov/pubmed/34971429
http://dx.doi.org/10.1007/s00018-021-04030-2
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