The Semi-Synthetic Peptide Lin-SB056-1 in Combination with EDTA Exerts Strong Antimicrobial and Antibiofilm Activity against Pseudomonas aeruginosa in Conditions Mimicking Cystic Fibrosis Sputum.

Giuseppantonio Maisetta,Ilaria Serra,Lucia Grassi,Andrea Rinaldi,Giovanna Batoni,Mariano Scorciapino,Semih Esin

doi:10.3390/ijms18091994

Abstract

Pseudomonas aeruginosa is a major cause of chronic lung infections in cystic fibrosis (CF) patients. The ability of the bacterium to form biofilms and the presence of a thick and stagnant mucus in the airways of CF patients largely contribute to antibiotic therapy failure and demand for new antimicrobial agents able to act in the CF environment. The present study investigated the anti-P. aeruginosa activity of lin-SB056-1, a recently described semi-synthetic antimicrobial peptide, used alone and in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA). Bactericidal assays were carried out in standard culture conditions and in an artificial sputum medium (ASM) closely resembling the CF environment. Peptide’s structure and interaction with large unilamellar vesicles in media with different ionic strengths were also investigated through infrared spectroscopy. Lin-SB056-1 demonstrated fast and strong bactericidal activity against both mucoid and non-mucoid strains of P. aeruginosa in planktonic form and, in combination with EDTA, caused significant reduction of the biomass of P. aeruginosa mature biofilms. In ASM, the peptide/EDTA combination exerted a strong bactericidal effect and inhibited the formation of biofilm-like structures of P. aeruginosa. Overall, the results obtained highlight the potential of the lin-SB056-1/EDTA combination for the treatment of P. aeruginosa lung infections in CF patients.

Highlights

Cystic fibrosis (CF) is a genetically inherited disease characterized by defects in the transport protein cystic fibrosis transmembrane conductance regulator (CFTR), causing the production of a sticky mucus that stands in the respiratory tract [1]
We evaluated the ability of the lin-SB056-1/ethylenediaminetetraacetic acid (EDTA) combination to inhibit the formation of biofilm-like structures (BLS) over the time
We evaluated the ability o6fotfh1e8 lin-SB056-1/EDTA combination to inhibit the formation of BLSs over the time

Summary

Introduction

Cystic fibrosis (CF) is a genetically inherited disease characterized by defects in the transport protein cystic fibrosis transmembrane conductance regulator (CFTR), causing the production of a sticky mucus that stands in the respiratory tract [1]. During the course of the infection, adaptation of P. aeruginosa to lung environment involves the shift from a non-mucoid to a mucoid phenotype that has been associated with a worse clinical prognosis [3]. Instead of the classical surface-attached communities, detected in most biofilm infections, in the CF airway, P. aeruginosa forms biofilms composed of small clusters of planktonic bacterial aggregates containing dead neutrophils [5]. These non-attached cell aggregates, referred to as biofilm-like structures (BLS), appear to share many properties with conventional surface-attached biofilms, including dependence on quorum sensing, presence of subpopulations of dormant cells (“persisters”), and resistance to antibiotics [6]

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Conclusion