Myxinidin-Derived Peptide against Biofilms Caused by Cystic Fibrosis Emerging Pathogens

Abstract

Chronic lung infections in cystic fibrosis (CF) patients are triggered by multidrug-resistant bacteria such as Pseudomonas aeruginosa, Achromobacter xylosoxidans, and Stenotrophomonas maltophilia. The CF airways are considered ideal sites for the colonization and growth of bacteria and fungi that favor the formation of mixed biofilms that are difficult to treat. The inefficacy of traditional antibiotics reinforces the need to find novel molecules able to fight these chronic infections. Antimicrobial peptides (AMPs) represent a promising alternative for their antimicrobial, anti-inflammatory, and immunomodulatory activities. We developed a more serum-stable version of the peptide WMR (WMR-4) and investigated its ability to inhibit and eradicate C. albicans, S. maltophilia, and A. xylosoxidans biofilms in both in vitro and in vivo studies. Our results suggest that the peptide is able better to inhibit than to eradicate both mono and dual-species biofilms, which is further confirmed by the downregulation of some genes involved in biofilm formation or in quorum-sensing signaling. Biophysical data help to elucidate its mode of action, showing a strong interaction of WMR-4 with lipopolysaccharide (LPS) and its insertion in liposomes mimicking Gram-negative and Candida membranes. Our results support the promising therapeutic application of AMPs in the treatment of mono- and dual-species biofilms during chronic infections in CF patients.

Strategic Single-Residue Substitution in the Antimicrobial Peptide Esc(1–21) Confers Activity against Staphylococcus aureus, Including Drug-Resistant and Biofilm Phenotype

“…An aliquot of the mixture was taken at each pre-established time point and MeCN was added to precipitate serum proteins. Then, the mixture was cooled to 4 °C, centrifuged for 15 min (13,000 g rpm), and then the supernatant was checked by HPLC using a Phenomenex Jupiter column (4 μm Proteo 90 Å 250 × 21.20 mm) with a linear gradient of MeCN (0.1% TFA) and H 2 O (0.1% TFA) from 10 to 90% in 20 min and with a flow rate of 1 mL/min . The percentage of the nondegraded peptide was calculated by integrating the peak area of each HPLC chromatogram.…”

A Re-Purposing Strategy: Sub-Lethal Concentrations of an Eicosanoid Derived from the Omega-3-Polyunsaturated Fatty Acid Resolvin D1 Affect Dual Species Biofilms

“…Polymicrobial biofilms found in almost all niches of the human body such as the oral cavity and gastrointestinal and urogenital tracts have been extensively studied although little is known about the behavior of mixed microorganism communities, particularly fungal-bacterial biofilms [ 2 ]. The formation of polymicrobial biofilms has been linked to a variety of human diseases, including oral cavity infection, otitis media, chronic lung infection, burn wounds, urinary tract infection, and medical device-related infection [ 4 , 5 , 6 , 7 , 8 ]. Several studies show that polymicrobial interactions result in increased tolerance to antimicrobial agents or in a variety of other environmental stress conditions and evade host immune responses.…”