Mecanismos inmunológicos en Cnidaria: Caracterización in silico de Péptidos antimicrobianos.

Abstract

Cnidarians are invertebrates that emerged 700 million years ago. They present a great complexity that is reflected in the genome of the immune system. The characterization of these defense mechanisms in Cnidarians has been possible thanks to genomic and transcriptomic analyses, which have shown the presence of several genes that encode immune response molecules conserved in vertebrates. For Cnidaria, various pathogen recognition receptors (PRR) have been described, signaling molecules that have the purpose of making the transcription of genes with immune functions effective, and effector molecules, whose objective is the elimination of the pathogen. Antimicrobial peptides favor the effector response against pathogens and are key molecules given their ability to act against fungi, viruses and bacteria. In addition, they are highly conserved and in Cnidaria they have bactericidal capacity, which makes them molecules that can be models for evolutionary and bioprospecting studies. The objective of this research was to structurally characterize antimicrobial peptides (AMP) belonging to the defensin family in different species of Cnidarians by computational analysis. To achieve this purpose, an exhaustive search was carried out for sequences homologous to antimicrobial peptides belonging to the defensin family in the proteomes available for Cnidarians, as well as 3D modeling by sequence homology and a functional characterization of the peptides with a tool developed under a machine learning approach. 3D homology modeling allowed the structural characterization of twelve peptides in 11 Cnidarian species, which showed structural similarity with defensins described in the species Nasonia vitripennis, Pisum sativum, Solanum lycopersicum and Aurelia aurita. These peptides were also evaluated for different physicochemical properties such as hydrophobic moment, hydrophobicity, net charge, amphiphilic index and isoelectric point, showing values that are ideal for AMP. The functional characterization showed bactericidal potential of 20 peptides against multiresistant bacteria Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. Finally, the construction of a phylogenetic tree was carried out, where it is evident that the Nuetrophil defensin, described in Homo sapiens, shares a close common ancestor with different peptides described in Cnidarians, characterized by showing a bactericidal potential and an α helix structure rich in cysteines (six), typical of mammalian and insect defensins. The results obtained show that Cnidaria present AMP with structural and physicochemical characteristics similar to those described in defensins of insects, mammals and plants. The structural characteristics of these peptides, their physicochemical properties and their functional potential outline them as promising molecules for the discovery of new antibiotics.