| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1944406 | Biochimica et Biophysica Acta (BBA) - Biomembranes | 2013 | 10 Pages |
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.
Graphical abstractAntimicrobial activity of a novel peptide by modifying N-terminal bovine lactoferrin against multidrug resistant gram-negative bacteria and fungi.Figure optionsDownload full-size imageDownload high-quality image (170 K)Download as PowerPoint slideHighlights► The peptide, L10 is a modified N-terminal of bovine lactoferrin. ► L10 inhibits the growth of gram-negative bacteria and C. albicans and C. parapsilosis. ► L10 acts via the membrane permeabilization. ► L10 inhibited endotoxin procoagulant activity. ► L10 binds with LA and exhibits anti-inflammatory activity by inhibiting COX-2.
