Abstract
Chronic respiratory infections are the main cause of morbidity and mortality in cystic fibrosis (CF) patients, and are characterized by the development of multidrug resistance (MDR) phenotype and biofilm formation, generally recalcitrant to treatment with conventional antibiotics. Hence, novel effective strategies are urgently needed. Antimicrobial peptides represent new promising therapeutic agents. Here, we analyze for the first time the efficacy of three versions of a cryptide identified in human apolipoprotein B (ApoB, residues 887-922) towards bacterial strains clinically isolated from CF patients. Antimicrobial and anti-biofilm properties of ApoB-derived cryptides have been analyzed by broth microdilution assays, crystal violet assays, confocal laser scanning microscopy and scanning electron microscopy. Cell proliferation assays have been performed to test cryptide effects on human host cells. ApoB-derived cryptides have been found to be endowed with significant antimicrobial and anti-biofilm properties towards Pseudomonas and Burkholderia strains clinically isolated from CF patients. Peptides have been also found to be able to act in combination with the antibiotic ciprofloxacin, and they are harmless when tested on human bronchial epithelial mesothelial cells. These findings open interesting perspectives to cryptide applicability in the treatment of chronic lung infections associated with CF disease.
Highlights
Cystic fibrosis (CF) is a rare autosomal recessive disease affecting 1 in 2500 newborns in Europe [1]
We demonstrate that the three apolipoprotein B (ApoB)-derived cryptides exert significant antimicrobial and anti-biofilm effects towards Pseudomonas and Burkholderia strains clinically isolated from CF patients and that they are able to act in combination with the ciprofloxacin antibiotic, widely used to treat chronic lung infections in CF patients [45]
We tested the ability of r(P)ApoBLPro, r(P)ApoBLAla and r(P)ApoBSPro to affect the biofilm of bacterial strains clinically isolated from CF patients
Summary
Cystic fibrosis (CF) is a rare autosomal recessive disease affecting 1 in 2500 newborns in Europe [1]. The concomitant decrease in the pharmaceutical industry research pipeline for novel antimicrobial agents during the last three decades has, resulted in an urgent need for the discovery of novel effective antimicrobial strategies [23] In this scenario, naturally occurring antimicrobial peptides (AMPs), or their derivatives, represent an appealing source for the generation of new therapeutic agents able to treat chronic MDR bacterial infections [24,25]. We demonstrate that the three ApoB-derived cryptides exert significant antimicrobial and anti-biofilm effects towards Pseudomonas and Burkholderia strains clinically isolated from CF patients and that they are able to act in combination with the ciprofloxacin antibiotic, widely used to treat chronic lung infections in CF patients [45]. ApoB-derived cryptides have been found to be not toxic when tested on
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