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Design of Bactericidal Peptides Against Escherichia coli O157:H7, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

[ Vol. 14 , Issue. 7 ]

Author(s):

Jenniffer Cruz, Paola Rondon-Villarreal, Rodrigo G. Torres, Mauricio Urquiza, Fanny Guzman, Claudio Alvarez, Maria Angeles Abengozar, Daniel A. Sierra, Luis Rivas, Roberto Fernandez-Lafuente and Claudia C. Ortiz*   Pages 741 - 752 ( 12 )

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 μ-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=25 μM) and Pseudomonas aeruginosa (MIC=10 μM). Peptide GIBIM-P5S9K caused permeabilization of the bacterial membrane at 25

Keywords:

Genetic algorithm, peptide design, antimicrobial peptides, pathogen bacterial, peptide synthesis, fluorescence microscopy.

Affiliation:

Grupo de Investigacion en Bioquimica y Microbiologia (GIBIM), Escuela de Quimica, Universidad Industrial de Santander, Edificio Camilo Torres 202, Bucaramanga, Grupo de Investigacion en Bioquimica y Microbiologia (GIBIM), Escuela de Quimica, Universidad Industrial de Santander, Edificio Camilo Torres 202, Bucaramanga, Grupo de Investigacion en Bioquimica y Microbiologia (GIBIM), Escuela de Quimica, Universidad Industrial de Santander, Edificio Camilo Torres 202, Bucaramanga, Grupo de Investigacion en Bioquimica y Microbiologia (GIBIM), Escuela de Quimica, Universidad Industrial de Santander, Edificio Camilo Torres 202, Bucaramanga, NBC Nucleo Biotecnologia Curauma, Pontificia Universidad Catolica de Valparaiso, Campus Curauma, Av. Universidad, 330 Valparaiso, NBC Nucleo Biotecnologia Curauma, Pontificia Universidad Catolica de Valparaiso, Campus Curauma, Av. Universidad, 330 Valparaiso, Centro de Investigaciones Biologicas (CIB-CSIC), Madrid, Grupo de Investigacion en Control, Electronica, Modelado y Simulacion (CEMOS), Universidad Industrial de Santander, Edificio Laboratorios Pesados, Bucaramanga, Centro de Investigaciones Biologicas (CIB-CSIC), Madrid, Departamento de Biocatalisis. ICP-CSIC, Campus UAM-CSIC Cantoblanco, Madrid, Grupo de Investigacion en Bioquimica y Microbiologia (GIBIM), Escuela de Microbiologia y Bioanalisis, Universidad Industrial de Santander, Edificio Camilo Torres 202, Bucaramanga



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