Effects of de novo designed peptides on bacterial envelop of escherichia coli and staphylococcus aureus

MATURANA PATRICIA; HOLLMANN, AXEL

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofisica

The emergence of multidrug-resistant bacteria has a direct impact on global publichealth. In this context, antimicrobial peptides (AMPs) represent an alternative due toexhibit a broad spectrum of antimicrobial activity (bacteria, fungi, parasites, viruses) anddo not easily induce resistance. In previous work, by using model membranes, westudied two related ?the novo? design peptides, P6 that show no antimicrobial activityand P6.2 witch exhibited good antibacterial activity. However, in order to a propercharacterization, effect on bacteria must be unraveled. In this context, we aimed tostudy the interaction of both peptides with whole bacteria using Escherichia coli andStaphylococcus aureus as a model.Zeta Potential experiments confirming that both peptides were able to interact with thenegative bacterial envelope of E. coli and S. aureus. However, the effects on P6.2 weremuch more noticeable in both bacteria. Then, the disrupt of the bacterial envelope wasasses by dynamic light scattering following the polydispersion index. A significantincrease in the dispersion of total particulates content was observed in both bacteriaafter being incubated only with P6.2, indicating disorganization of bacteria structure.The ability of both peptides to disrupt the bacterial membrane was also evaluated. Inthe case of E. coli, the outer (OM) and inner (IM) membrane permeabilization wereanalyzed. Beside both peptides were able to induce damage in the OM, 6 times fold ofP6 was needed in order to obtain comparable results than those obtained with P6.2.When IM disruption was evaluated, a similar trend was observed, P6.2 not only exhibitsmore product formation, implying a greater disruption of the membrane but a fasterkinetic. In the case of S. aureus, both peptides were able to permeabilize the plasmaticmembrane, but the effects were much more noticeable with the P6.2. When membranepermeabilization data were compared in both bacteria, E. coli showed faster kinetics anda lower amount of peptide was needed to obtain similar results.All data together allows postulating, in a physiologic model, that the poorer affinity of P6for bacterial envelope results in a lower concentration final of the peptide in the bacterialmembrane, insufficient to cause enough membrane damage capable of triggeringbacterial death.