Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical Isolates and Their Potential Molecular Targets
Sandra Patricia Rivera-Sánchez,
Helen Astrid Agudelo-Góngora,
José Oñate-Garzón,
Liliana Janeth Flórez-Elvira,
Adriana Correa,
Paola Andrea Londoño,
Juan David Londoño-Mosquera,
Alberto Aragón-Muriel,
Dorian Polo-Cerón,
Iván Darío Ocampo-Ibáñez
Affiliations
Sandra Patricia Rivera-Sánchez
Research Group of Microbiology, Industry and Environment, Faculty of Basic Sciences, Universidad Santiago de Cali, Cali 760035, Colombia
Helen Astrid Agudelo-Góngora
Research Group of Microbiology, Industry and Environment, Faculty of Basic Sciences, Universidad Santiago de Cali, Cali 760035, Colombia
José Oñate-Garzón
Research Group of Chemical and Biotechnology, Faculty of Basic Sciences, Universidad Santiago de Cali, Cali 760035, Colombia
Liliana Janeth Flórez-Elvira
Department of Public Health and Community Medicine, Universidad Icesi, Cali 760032, Colombia
Adriana Correa
Research Group of Microbiology, Industry and Environment, Faculty of Basic Sciences, Universidad Santiago de Cali, Cali 760035, Colombia
Paola Andrea Londoño
Laboratorio de Salud Pública Departamental, Secretaria Departamental de Salud del Valle del Cauca, Gobernación del Valle del Cauca, Cali 760045, Colombia
Juan David Londoño-Mosquera
Laboratorio de Investigación en Catálisis y Procesos (LICAP), Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad del Valle, Cali 760001, Colombia
Alberto Aragón-Muriel
Laboratorio de Investigación en Catálisis y Procesos (LICAP), Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad del Valle, Cali 760001, Colombia
Dorian Polo-Cerón
Laboratorio de Investigación en Catálisis y Procesos (LICAP), Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad del Valle, Cali 760001, Colombia
Iván Darío Ocampo-Ibáñez
Research Group of Microbiology, Industry and Environment, Faculty of Basic Sciences, Universidad Santiago de Cali, Cali 760035, Colombia
Antimicrobial resistance reduces the efficacy of antibiotics. Infections caused by multidrug-resistant (MDR), Gram-negative bacterial strains, such as Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), are a serious threat to global health. However, cationic antimicrobial peptides (CAMPs) are promising as an alternative therapeutic strategy against MDR strains. In this study, the inhibitory activity of a cationic peptide, derived from cecropin D-like (ΔM2), against MDRKp and MDRPa clinical isolates, and its interaction with membrane models and bacterial genomic DNA were evaluated. In vitro antibacterial activity was determined using the broth microdilution test, whereas interactions with lipids and DNA were studied by differential scanning calorimetry and electronic absorption, respectively. A strong bactericidal effect of ΔM2 against MDR strains, with minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) between 4 and 16 μg/mL, was observed. The peptide had a pronounced effect on the thermotropic behavior of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) membrane models that mimic bacterial membranes. Finally, the interaction between the peptide and genomic DNA (gDNA) showed a hyperchromic effect, which indicates that ΔM2 can denature bacterial DNA strands via the grooves.