A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: Design, synthesis, activity against multidrug-resistant bacteria and Candida

Biswajit Mishra, Geeta Devi Leishangthem, Kamaldeep Gill, Abhay K. Singh, Swagata Das, Kusum Singh, Immaculata Xess, Amit Dinda, Arti Kapil, Ishan K. Patro, Sharmistha Dey

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageEnglish
Pages (from-to)677-686
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1828
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Anti-inflammatory
  • Antimicrobial peptide
  • Cyclooxygenase
  • Extended spectrum beta lactamase
  • Lactoferrin
  • Surface plasmon resonance

Fingerprint

Dive into the research topics of 'A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: Design, synthesis, activity against multidrug-resistant bacteria and Candida'. Together they form a unique fingerprint.

Cite this