info:eu-repo/semantics/article
Integrating In Vitro and In Silico Analysis of a Cationic Antimicrobial Peptide Interaction with Model Membranes of Colistin-Resistant Pseudomonas aeruginosa Strains
Registro en:
10.3390/pharmaceutics14061248
1999-4923
Autor
Manrique Moreno, Marcela María
Rivera Sanchez, Sandra Patricia
Ocampo Ibáñez, Iván Darío
Liscano, Yamil
Martínez, Natalia
Muñoz, Isamar
Martinez Martinez, Luis
Oñate Garzon, José
Institución
Resumen
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 ∆M2 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 palmitoyloleyl-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. COL0156275