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.

Lactobacillus pentosus expressing porcine lactoferrin elevates antibacterial activity and improves the efficacy of vaccination against Aujeszky’s disease

“…Many studies have shown that the biological properties of LF are closely associated with the N-lobe (Mishra et al, 2013). In this study, the N-terminal of porcine lactoferrin gene was expressed using a Lactobacillus secretion expression vector and the resulting recombinant protein exhibited antibacterial activity against Escherichia coli, Salmonella enterica ssp.…”

Biological Properties and Characterization of ASL50 Protein from Aged Allium sativum Bulbs

“…The samples were processed according to the method described by Mishra et al [14]. The sections were observed under a Morgagni-268 electron microscope under standard operating conditions.…”

Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides

“…L10 was further tested against 30 multidrug-resistant isolates of extended spectrum β-lactamase (ESBLs) producing bacteria, including P. aeruginosa, K. pneumoniae and Acinobacter species with the MICs reported to be in the range of 1-8 µg/ml, while also having an MIC of 6.25 µg/ml against C. albicans. In addition L10 showed no hemolytic activity, even at high concentrations of 800 µg/ml [126].…”