The Ancestral N-Terminal Domain of Big Defensins Drives Bacterially Triggered Assembly into Antimicrobial Nanonets

Big defensins, ancestors of β-defensins, are composed of a β-defensin-like C-terminal domain and a globular hydrophobic ancestral N-terminal domain. This unique structure is found in a limited number of phylogenetically distant species, including mollusks, ancestral chelicerates, and early-branching...

Full description

Bibliographic Details
Published in:mBio
Main Authors: Loth, Karine, Vergnes, Agnès, Barreto, Cairé, Voisin, Sébastien N., Meudal, Hervé, Da Silva, Jennifer, Bressan, Albert, Belmadi, Nawal, Bachère, Evelyne, Aucagne, Vincent, Cazevielle, Chantal, Marchandin, Hélène, Rosa, Rafael Diego, Bulet, Philippe, Touqui, Lhousseine, Delmas, Agnès F., Destoumieux-Garzón, Delphine
Format: Text
Language:English
Published: American Society for Microbiology 2019
Subjects:
Research Article
Crassostrea gigas
Online Access:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805989/
http://www.ncbi.nlm.nih.gov/pubmed/31641083
https://doi.org/10.1128/mBio.01821-19
Description
Summary:Big defensins, ancestors of β-defensins, are composed of a β-defensin-like C-terminal domain and a globular hydrophobic ancestral N-terminal domain. This unique structure is found in a limited number of phylogenetically distant species, including mollusks, ancestral chelicerates, and early-branching cephalochordates, mostly living in marine environments. One puzzling evolutionary issue concerns the advantage for these species of having maintained a hydrophobic domain lost during evolution toward β-defensins. Using native ligation chemistry, we produced the oyster Crassostrea gigas BigDef1 (Cg-BigDef1) and its separate domains. Cg-BigDef1 showed salt-stable and broad-range bactericidal activity, including against multidrug-resistant human clinical isolates of Staphylococcus aureus. We found that the ancestral N-terminal domain confers salt-stable antimicrobial activity to the β-defensin-like domain, which is otherwise inactive. Moreover, upon contact with bacteria, the N-terminal domain drives Cg-BigDef1 assembly into nanonets that entrap and kill bacteria. We speculate that the hydrophobic N-terminal domain of big defensins has been retained in marine phyla to confer salt-stable interactions with bacterial membranes in environments where electrostatic interactions are impaired. Those remarkable properties open the way to future drug developments when physiological salt concentrations inhibit the antimicrobial activity of vertebrate β-defensins.

Similar Items