The research team has identified a frog skin derived antimicrobial peptide (AMP), Esc(1-21), which kills Pseudomonas aeruginosa with a membrane-perturbing activity that prevents bacteria from developing resistance. Furthermore, its analog containing two D-amino acids was found to be more efficient in reducing bacterial burden in murine models of P. aeruginosa lung infection, especially when encapsulated into polymeric nanoparticles (NPs). This project has carried out a multidisciplinary approach to explore the effect of the selected Esc peptides on the ion currents mediated by delF508-CFTR and to evaluate the pulmonary safety profile of the NPs and the host response upon in mice. The researchers demonstrated that both peptides are able (i) to increase the CFTR funcionality in cell lines expressing delF508-CFTR by direct interaction with the mutated protein and (ii) to increase chloride ions current in primary bronchial epithelial cells homozygous for the same mutation, by promoting the channel activity. This effect is comparable to that of genistein. Remarkably, such potentiator activity of CFTR was not explored previously for any AMP. In addition, the researchers discovered that Esc peptides and polyvinyl alcohol-engineered poly(lactic-co-glycolic) acid NPs do not alter the number of lung inflammatory cells in healthy mice or the global expression of lung epithelial genes, in contrast with the significant genetic changes provoked by colistin. Unlike clinically used CFTR modulators, Esc peptides would give particular benefit to CF patients by combining their capability to treat lung infections and to promote airway epithelium wound repair with the ability to restore the activity of CFTR with conductance defects. This can open the avenue for a new up-and-coming pharmacological approach, likely based on inhalable peptide-loaded NPs, to address CF lung disease.

Pubblications

• Ferrera L, Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides, Cellular and molecular life sciences vol. 79,1 67. 31 Dec. 2021
• Mangoni ML, Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation International, International journal of molecular sciences vol. 22,2 557. 8 Jan. 2021
• Mangoni ML, Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides, Current protein & peptide science vol. 21,4 (2020): 429-438

Abstract 

• Mangoni ML, Immunomodulatory activities of ESC peptides in lung infection, 61° SIB Meeting Virtual Edition, 23-24 September 2021 2021

Patents

• Mangoni Maria Luisa WO2021074025A1 USE OF ESCULENTIN AND ITS DERIVATIVES FOR USE IN THE TREATMENT OF CYSTIC FIBROSIS FFC 2019/08 Dip. Scienze Biochimiche, Univ. “La Sapienza”, Roma