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The antimicrobial potential of a new derivative of cathelicidin from <Emphasis Type="Italic">Bungarus fasciatus</Emphasis> against methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>
Authors:Mercedeh Tajbakhsh  Abdollah Karimi  Abolghasem Tohidpour  Naser Abbasi  Fatemeh Fallah  Maziar Mohammad Akhavan
Institution:1.Pediatric Infections Research Center (PIRC), Research Institute for Children health,Shahid Beheshti University of Medical Sciences,Tehran,Iran;2.Research Institute of Molecular Medicine and Pathobiochemistry,Krasnoyarsk State Medical University,Krasnoyarsk,Russia;3.Department of Pharmacology, Faculty of Medicine,Ilam University of Medical Sciences,Ilam,Iran;4.Biotechnology and Medicinal Plants Research Center,Ilam University of Medical Sciences,Ilam,Iran;5.Skin Research Center,Shahid Beheshti University of Medical Sciences,Tehran,Iran;6.Department of Pharmacology, Medical School,Iran University of Medical Sciences,Tehran,Iran
Abstract:Cathelicidins are a family of antimicrobial peptides which exhibit broad antimicrobial activities against antibiotic-resistant bacteria. Considering the progressive antibiotic resistance, cathelicidin is a candidate for use as an alternative approach to treat and overcome the challenge of antimicrobial resistance. Cathelicidin-BF (Cath-BF) is a short antimicrobial peptide, which was originally extracted from the venom of Bungarus fasciatus. Recent studies have reported that Cath-BF and some related derivatives exert strong antimicrobial and weak hemolytic properties. This study investigates the bactericidal and cytotoxic effects of Cath-BF and its analogs (Cath-A and Cath-B). Cath-A and Cath-B were designed to increase their net positive charge, to have more activity against methicillin resistant S. aureus (MRSA). The results of this study show that Cath-A, with a +17-net charge, has the most noteworthy antimicrobial activity against MRSA strains, with minimum inhibitory concentration (MIC) ranging between 32–128 μg/ml. The bacterial kinetic analysis by 1 × MIC concentration of each peptide shows that Cath-A neutralizes the clinical MRSA isolate for 60 min. The present data support the notion that increasing the positive net charge of antimicrobial peptides can increase their potential antimicrobial activity. Cath-A also displayed the weakest cytotoxicity effect against human umbilical vein endothelial and H9c2 rat cardiomyoblast cell lines. Analysis of the hemolytic activity reveals that all three peptides exhibit minor hemolytic activity against human erythrocytes at concentrations up to 250 μg/ml. Altogether, these results suggest that Cath-A and Cath-B are competent candidates as novel antimicrobial compounds against MRSA and possibly other multidrug resistant bacteria.
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