Journal Article

Potassium Efflux Induced by a New Lactoferrin-Derived Peptide Mimicking the Effect of Native Human Lactoferrin on the Bacterial Cytoplasmic Membrane

Pérez-Gil, J., Andrés, M. T., Fierro, J. F., Sánchez, M., Viejo-Diaz, M.

2003

Overview

A 31-amino acid synthetic peptide (NH(2)-FFSASCVPGADKGQFPNLCRLCAGTGENKCA-COOH) was chemically synthesized based on the amino acid sequence of a region of human lactoferrin homologous to other sequences present in the N- and C-lobes of all members of the transferrin family proteins. The peptide, termed kaliocin-1, and lactoferrin showed a bactericidal effect in assays performed in low-ionic-strength conditions. This is the first time that it is shown that the antimicrobial effect of lactoferrin depends on the extracellular cation concentration. The antimicrobial effect of kaliocin-1 was lower than that of human lactoferrin, but their activities were inhibited by Na(+) or K(+) in a cation concentration-dependent manner. In addition, the peptide was able to mimic native lactoferrin, inducing K(+)-efflux and a selective dissipation of the transmembrane electrical potential of Escherichia coli cells without causing extensive damage to the outer and inner bacterial membranes. In contrast, the peptide, but not lactoferrin, was able to permeabilize different ions through liposomal membranes. The hypothetical interaction of kaliocin-1 with a bacterial membrane compound is discussed based in the different ion flux induced on cellular and artificial membranes as well as data from circular dichroism assays. Kaliocin-1 was not cytotoxic and could be a suitable model for the design of analogs able to mimic the antibacterial effect of human lactoferrin.

• Publisher: Springer Nature B.V
• Subject: Amino Acid Sequence / Amino acids / Animals / Anti-Bacterial Agents - chemistry / Anti-Bacterial Agents - pharmacology / Bacteria / Biomimetic Materials - chemistry / Biomimetic Materials - pharmacology / Cell Membrane - drug effects / Cell Membrane - metabolism / Cell Membrane Permeability - drug effects / Circular Dichroism / E coli / Escherichia coli / Escherichia coli - drug effects / Escherichia coli - metabolism / Gram-Negative Bacteria - drug effects / Gram-Negative Bacteria - metabolism / Gram-Positive Bacteria - drug effects / Gram-Positive Bacteria - metabolism / Humans / Lactoferrin - analogs & derivatives / Lactoferrin - pharmacology / Liposomes - metabolism / Membrane Potentials - drug effects / Membranes / Mice / Microbiology / Molecular Sequence Data / Peptides / Peptides - chemistry / Peptides - pharmacology / Potassium - chemistry / Potassium - metabolism / Potassium - pharmacology / Proteins / Rabbits / Sequence Homology, Amino Acid / Sodium - chemistry / Sodium - pharmacology / Transferrin - genetics