The first stage of the action mechanism of small cationic peptides with antimicrobial activity is ruled by electrostatic interactions between the peptide and the pathogen cell membrane. Thus, an increase in its activity could be expected with an increase in the positive charge on the peptide. By contrast, the opposite behavior has been observed when the charge increases to reach a critical value, beyond which the activity falls. This work studies the perturbation effects in a cell membrane model for two small cationic peptides with similar length and morphology but with different cationic charges. The synthesis and antibacterial activity of the two peptides used in this study are described. The thermodynamic study associated with the insertion of these peptides into the membrane and the perturbing effects on the bilayer structure provide valuable insights into the molecular action mechanism associated with the charge of these small cationic peptides.

Pathogenic bacteria have the ability to develop antibiotic resistance mechanisms. Their action consists mainly in the production of bacterial enzymes that inactivate antibiotics or the appearance of modifications that prevent the arrival of the drug at the target point or the alteration of the target point itself, becoming a growing problem for health systems. Chitosan–gold nanoparticles (Cs-AuNPs) have been shown as effective bactericidal materials avoiding damage to human cells. In this work, Cs-AuNPs were synthesized using chitosan as the reducing agent, and a systematic analysis of the influence of the synthesis parameters on the size and zeta potential of the Cs-AuNPs and their UV-vis spectra was carried out. We used a simulation model to characterize the interaction of chitosan with bacterial membranes, using a symmetric charged bilayer and two different chitosan models with different degrees of the chitosan amine protonation as a function of pH, with the aim to elucidate the antibacterial mechanism involving the cell wall disruption. The Cs-AuNP antibacterial activity was evaluated to check the simulation model.