Puede utilizar el filtro de búsqueda del panel izquierdo para acotar los resultados
Filtro
Tipo de publicación
Todos Libros Revistas
Título
Autor
Palabras clave
ISBN
Acceso DOI
Acceso digital CSIC
Buscar
Datos técnicos
RevistaMedicinal chemistry
Año2018
Volumen14
Páginas741 – 752
Internacional

Design of bactericidal peptides against Escherichia coli O157:H7, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

Autores:Roberto Fernandez-Lafuente
Grupos de investigación:Optimización de biocatalizadores y bioprocesos enzimáticos
Jenniffer Cruza, Paola Rondón-Villarreala,b, Rodrigo G. Torresa, Mauricio Urquizaa,c, Fanny Guzmánd, Claudio Alvarezd,e, María Ángeles Abengózarf, Daniel A. Sierrab, Luis Rivasf, Roberto Fernández-Lafuenteg and Claudia C. Ortiz h,*
a Grupo de Investigación en Bioquímica y Microbiología (GIBIM), Escuela de Química, Universidad Industrial de Santander, Edificio Camilo Torres 202, Bucaramanga, Colombia; b Grupo de Investigación en Control, Electrónica, Modelado y Simulación (CEMOS), Universidad Industrial de Santander, Edificio Laboratorios Pesados, Bucaramanga, Colombia; c Departamento de Química, Universidad Nacional de Colombia, Cra 30 # 45-03, 111321 Bogotá, Colombia,  d NBC Núcleo Biotecnología Curauma, Pontificia Universidad Católica de Valparaíso, Campus Curauma, Av. Universidad, 330 Valparaíso, Chile; e Centro de Estudios Avanzados en Zonas Áridas, Coquimbo, Chile; f Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain; g Departamento de Biocatálisis. ICP-CSIC, Campus UAM-CSIC Cantoblanco, Madrid. Spain; h Grupo de Investigación en Bioquímica y Microbiología (GIBIM), Escuela de Microbiología y Bioanálisis, Universidad Industrial de Santander, Edificio Camilo Torres 202, Bucaramanga, Colombia.



Abstract: Background: Antimicrobial peptides are on the first line of defense against pathogenic microorganisms of many living beings. These compounds are considered natural antibiotics that can overcome bacterial resistance to conventional antibiotics. Due to this characteristic, new peptides with improved properties are quite appealing for designing new strategies for fighting pathogenic bacteria Methods: Sixteen designed peptides were synthesized using Fmoc chemistry; five of them are new cationic antimicrobial peptides (CAMPs) designed using a genetic algorithm that optimizes the antibacterial activity based on selected physicochemical descriptors and 11 analog peptides derived from these five peptides were designed and constructed by single amino acid substitutions. These 16 peptides were structurally characterized and their biological activity was determined against Escherichia coli O157:H7 (E. coli O157:H7), and methicillin-resistant strains of Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) were determined Results: These 16 peptides were folded into an α-helix structure in membrane-mimicking environment. Among these 16 peptides, GIBIM-P5S9K (ATKKCGLFKILKGVGKI) showed the highest antimicrobial activity against E. coli O157:H7 (MIC=10µM), methicillin resistant Staphylococcus aureus (MRSA) (MIC=25µM) and Pseudomonas aeruginosa (MIC=10 µM). Peptide GIBIM-P5S9K caused permeabilization of the bacterial membrane at 25 µM as determined by the Sytox Green uptake assay and the labelling of these bacteria by using the fluoresceinated peptide. GIBIM-P5S9K seems to be specific for these bacteria because at 50 µM provoked lower than 40% of erythrocyte hemolysis. Conclusion: New CAMPs have been designed using a genetic algorithm based on selected physicochemical descriptors and single amino acid substitution. These CAMPs interacted quite specifically with the bacterial cell membrane, GIBIM-P5S9K exhibiting high antibacterial activity on Escherichia coli O157:H7, methicillin resistant strains of Staphylococcus aureus and P. aeruginosa
Palabras clave:peptide design, antimicrobial peptides, genetic algorithm, pathogen bacterial, peptide synthesis, fluorescence microscopy
logo de CSIC