title: A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: design, synthesis, activity against multidrug-resistant bacteria and Candida.
abstract: Lactoferrin (LF) is believed to contribute to the host's defense against microbial infections. This work focuses on the antibacterial and antifungal activities of a designed peptide, L10 (WFRKQLKW) by modifying the first eight N-terminal residues of bovine LF by selective homologous substitution of amino acids on the basis of hydrophobicity, L10 has shown potent antibacterial and antifungal properties against clinically isolated extended spectrum beta lactamases (ESBL), producing gram-negative bacteria as well as Candida strains with minimal inhibitory concentrations (MIC) ranging from 1 to 8 μg/mL and 6.5 μg/mL, respectively. The peptide was found to be least hemolytic at a concentration of 800 μg/mL. Interaction with lipopolysaccharide (LPS) and lipid A (LA) suggests that the peptide targets the membrane of gram-negative bacteria. The membrane interactive nature of the peptide, both antibacterial and antifungal, was further confirmed by visual observations employing electron microscopy. Further analyses, by means of propidium iodide based flow cytometry, also supported the membrane permeabilization of Candida cells. The peptide was also found to possess anti-inflammatory properties, by virtue of its ability to inhibit cyclooxygenase-2 (COX-2). L10 therefore emerges as a potential therapeutic remedial solution for infections caused by ESBL positive, gram-negative bacteria and multidrug-resistant (MDR) fungal strains, on account of its multifunctional activities. This study may open up new approach to develop and design novel antimicrobials.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Mishra
authors.forename: Geeta Devi
authors.initials: GD
authors.lastname: Leishangthem
authors.forename: Kamaldeep
authors.initials: K
authors.lastname: Gill
authors.forename: Abhay K
authors.initials: AK
authors.lastname: Singh
authors.forename: Swagata
authors.initials: S
authors.lastname: Das
authors.forename: Kusum
authors.initials: K
authors.lastname: Singh
authors.forename: Immaculata
authors.initials: I
authors.lastname: Xess
authors.forename: Amit
authors.initials: A
authors.lastname: Dinda
authors.forename: Arti
authors.initials: A
authors.lastname: Kapil
authors.forename: Ishan K
authors.initials: IK
authors.lastname: Patro
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Dey
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002175:Candida / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004912:Erythrocytes / Q000187:drug effects / Q000382:microbiology; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D007781:Lactoferrin / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron / Q000379:methods; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D013997:Time Factors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D010455:Peptides; D007781:Lactoferrin; D001618:beta-Lactamases