Study of the Membrane Activity of the Synthetic Peptide ∆M3 Against Extended-Spectrum β-lactamase Escherichia coli Isolates

TL;DR

This study shows that the synthetic peptide ΔM3 effectively targets drug-resistant E. coli without harming human cells, likely by disrupting bacterial membranes.

Contribution

The novel contribution is the evaluation of ΔM3's membrane activity against extended-spectrum β-lactamase-producing E. coli isolates.

Findings

ΔM3 is active against E. coli isolates at concentrations similar to Meropenem.

The peptide showed no cytotoxicity in HaCaT keratinocyte cells.

ΔM3 interacts with bacterial membrane lipids, causing permeabilization.

Abstract

Escherichia coli is the most common microorganism causing nosocomial or community-acquired bacteremia, and extended-spectrum β-lactamase-producing Escherichia coli isolates are identified worldwide with increasing frequency. For this reason, it is necessary to evaluate potential new molecules like antimicrobial peptides. They are recognized for their biological potential which makes them promising candidates in the fight against infections. The goal of this research was to evaluate the potential of the synthetic peptide ΔM3 on several extended-spectrum β-lactamase producing E. coli isolates. The antimicrobial and cytotoxic activity of the peptide was spectrophotometrically determined. Additionally, the capacity of the peptide to interact with the bacterial membrane was monitored by fluorescence microscopy and infrared spectroscopy. The results demonstrated that the synthetic peptide is active against Escherichia coli isolates at concentrations similar to Meropenem. On the other hand, no cytotoxic effect was observed in HaCaT keratinocyte cells even at 10 times the minimal inhibitory concentration. Microscopy results showed a permeabilizing effect of the peptide on the bacteria. The infrared results showed that ΔM3 showed affinity for the lipids of the microorganism’s membrane. The results suggest that the ∆M3 interacts with the negatively charged lipids from the E. coli by a disturbing effect on membrane. Finally, the secondary structure experiments of the peptide showed a random structure in solution that did not change during the interaction with the membranes.

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