Integrating In Vitro and In Silico Analysis of a Cationic Antimicrobial Peptide Interaction with Model Membranes of Colistin-Resistant Pseudomonas aeruginosa Strains

Abstract

Bacterial antibiotic resistance is a serious global public health concern. Infections caused by colistin-resistant Pseudomonas aeruginosa (CRPa) strains represent a serious threat due to their considerable morbidity and mortality rates, since most of the current empirical antibiotic therapies are ineffective against these strains. Accordingly, cationic antimicrobial peptides (CAMPs) have emerged as promising alternatives to control resistant bacteria. In this study, the interaction of a CAMP derived from cecropin D-like (∆M2) with model membranes mimicking bacterial biomembranes of wild-type (WTPa) strains of P. aeruginosa and CRPa was evaluated through in vitro and in silico approaches. In vitro interaction was determined by infrared spectroscopy, whereas in silico molecular dynamics was performed to predict specific interactions between amino acids of ∆M2 and lipids of model membrane systems. Experimental analysis showed this peptide interacted with the lipids of bacterial-like model membranes of WTPa and CRPa. In both cases, an increase in the concentration of peptides induced an increase in the phase transition temperature of the lipid systems. On the other hand, the peptides in solution underwent a transition from a random to a helical secondary structure after interacting with the membranes mostly favored in the CRPa system. The α-helix structure percentage for ΔM2 interacting with WTPa and CRPa lipid systems was 6.4 and 33.2%, respectively. Finally, molecular dynamics showed ∆M2 to have the most affinities toward the phospholipids palmitoyl-oleyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) that mimic membranes of WTPa and CRPa, respectively. This work provides clues for elucidating the membrane-associated mechanism of action of ∆M2 against colistin-susceptible and -resistant strains of Pseudomonas aeruginosa.

Multi-Level Biological Network Analysis and Drug Repurposing Based on Leukocyte Transcriptomics in Severe COVID-19: In Silico Systems Biology to Precision Medicine

“…In the bioinformatics and precision medicine era, systems biology and multi-omics studies allow translational medicine to be effective in clinical practices [ 35 ]. Several combined wet and dry experimental studies have provided invaluable information in molecular biology and medicine [ 36 , 37 , 38 ]. Moreover, a combination of knowledge between biology, computer science, statistics, and mathematics explores the underlying molecular mechanisms of numerous diseases such as cancer, degenerative diseases, genetic diseases, etc.…”

In Vivo and In Vitro Evaluation of the Antibacterial Activity of the Synthetic Peptide LyeTx I mn∆K, Derived From <em>Lycosa erythrognatha</em> Spider Toxin, Against Methicillin-Resistant <em>Staphylococcus aureus</em> (MRSA)

“…Interestingly, above this critical concentration, the PDI values ramp up (>0.3) and two size populations were noted. This suggests that the peptide adsorption to the membranes is followed by vesicle aggregation at high peptide concentration (>20 µM) [22,47]. Notably, the peptide concentration dependence is also observed in the ζ-potential measurements.…”

The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo

“…Interestingly, above this critical concentration, the PDI values ramp up (>0.3) and two size populations were noted. This suggests that the peptide adsorption to the membranes is followed by vesicle aggregation at high peptide concentration (>20 μM) [ 22 , 47 ]. Notably, the peptide concentration dependence is also observed in the ζ-potential measurements.…”