Metal coordination governs the antimicrobial efficacy of calcitermin derivatives

Abstract

Antimicrobial peptides are promising alternatives to classical antibiotics. Their microbicidal activity can arise from different mechanisms, one of which is known as nutritional immunity and has metal micronutrients and metal-binding biomolecules as its main players. Calcitermin is an antimicrobial peptide and an effective metal-chelator. Its properties as antibacterial and anti-Candida agent have been recently studied both as free peptide and in presence of zinc and copper ions, with which it forms stable complexes. Calcitermin derivatives have also gained attractiveness thanks to the possibility of improving their properties, like metal-binding affinity and/or stability in biological fluids, through ad-hoc modifications of the native peptide sequence. In this work, the Ala-to-Ser substitutions close to the coordination site of calcitermin have been introduced to study the impact on the biological activity and metal-binding properties. Our results show that the metal coordination has a clear impact on the bioactivity of the studied compounds, to the point that also the truncated fragment of calcitermin, solely containing the main metal-binding residues, shows antimicrobial activity.