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.

Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides / Ferrera, L.; Cappiello, F.; Loffredo, M. R.; Puglisi, E.; Casciaro, B.; Botta, B.; Galietta, L. J. V.; Mori, M.; Mangoni, M. L.. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - 79:1(2022), p. 67. [10.1007/s00018-021-04030-2]

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

Ferrera L.
Primo
;
Cappiello F.
Secondo
;
Loffredo M. R.;Puglisi E.;Casciaro B.;Botta B.;Mangoni M. L.
Ultimo
2022

Abstract

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.
Antibiotic-resistance; Antimicrobial peptides; CFTR potentiators; Innate immunity; Lung pathology; Pulmonary drug delivery; Animals; Anti-Bacterial Agents; Antimicrobial Peptides; Bicarbonates; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Ion Transport; Lung Diseases; Pseudomonas Infections; Pseudomonas aeruginosa; Rats; Rats, Inbred F344
01 Pubblicazione su rivista::01a Articolo in rivista
Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides / Ferrera, L.; Cappiello, F.; Loffredo, M. R.; Puglisi, E.; Casciaro, B.; Botta, B.; Galietta, L. J. V.; Mori, M.; Mangoni, M. L.. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - 79:1(2022), p. 67. [10.1007/s00018-021-04030-2]
File allegati a questo prodotto
File Dimensione Formato  
Feerera_Esc peptides_2022.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.97 MB
Formato Adobe PDF
1.97 MB Adobe PDF Visualizza/Apri PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1610735
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 2
social impact