Esc peptides for novel therapeutics against Pseudomonas aeruginosa pulmonary infections: beyond antimicrobial activity
Year: 2024
Type: conference-abstract
Abstract: Esc peptides for novel therapeutics against Pseudomonas aeruginosa pulmonary infections: beyond antimicrobial activity Recently, the ability of Esc peptides to increase the F508del CFTR-mediated transepithelial conductance (TEEC) was studied in combination with FSK.This effect was higher for Esc-1C at 10 µM and comparable to that of GEN when used at the same concentration (Figure 2).We also found that this effect is highly dependent on the primary structure of Esc peptides and the presence of Ser-17 (Figure 3).The CFTR potentiating activity of Esc peptides was well preserved in primary airway epithelial cells from homozygous F508del patients (Figure 4).To verify whether the effect of Esc peptides on the ion currents was controlled by CFTR, patch clamp experiments (inside-out configuration) were carried out on Fisher Rat Thyroid cells (FRT) expressing F508del CFTR.The increased peptide-induced ion current is due to activation of CFTR and likely mediated by direct interaction of the peptides with CFTR (Figure 5).To achieve the lungs, it is fundamental the development of pharmaceutical formulations able to assist the peptide diffusion through extracellular barriers and to provide a gradual peptide release at the infectious site.Peptide-loaded PLGA-PVA nanoparticles (NPs) were able to improve the diffusion of the encaspulated peptide through the bronchial mucus and simulated biofilm (Figure 6).Note also that peptide-loaded NPs were found to be more efficient in reducing the number of P. aeruginosa in a mouse model of acute lung infection compared to the results found when the peptides were i.t.instilled in their soluble free form (Figure 7).CFTR-DEPENDENT TRANSEPITHELIAL CONDUCTANCE (G) BY ANALOGS OF ESC PEPTIDES CFTR-DEPENDENT TRANSEPITHELIAL
Source: European Peptide Symposium (EPS)
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4402843989