Contribuições à Toxinologia de Formigas do Cerrado pela caracterização e bioprospecção de suas peçonhas e moléculas - uma abordagem experimental e in silico

Abstract

Animal venoms are an established source of drugs, yet the field concentrates on snakes, scorpions and spiders, while ants, the richest lineage of venomous animals, remain underexplored, constrained by minute venom yields and by the gap between the abundance of omics data and the confirmed function of the molecules. The general aim of this thesis was to characterize and bioprospect the biotechnological and therapeutic potential of the venoms of Cerrado ants (and of their associated molecules and symbionts) through an integrated, experimental and in silico approach. Organized as a compilation of ten articles, it comprises three foundational reviews (methods in toxinology; the Brazilian contribution to ant toxinology; the ant microbiome), two systematic reviews on value and translation (the animal-toxin patent landscape; conservation as a bioeconomic strategy under the access-and-benefit-sharing regime), two experimental characterization studies, one computational study and two therapeutic-validation studies. Methods spanned biochemical, enzymatic and functional venom assays, mass spectrometry, a bioinformatics pipeline for sequence-based function prediction, and in vitro and in vivo assays of antimicrobial, immunomodulatory, antinociceptive and safety endpoints. Key results include the first toxinological characterizations of Neoponera foetida and Odontomachus haematodus, two Cerrado Ponerinae whose enzymatically rich venoms differ in function according to each species' ecology; an in silico pipeline that prioritized Hymenoptera peptides and highlighted ant dinoponeratoxins and ponericins as selective candidates; and the demonstration that the monomerized, non-lytic ectatomin subunits ET1A and ET1B are bactericidal against multidrug-resistant strains, restrain neutrophil extracellular trap formation without cytotoxicity, show antinociceptive potential in Drosophila melanogaster larvae, and are safe in the chick-embryo model. We conclude that Cerrado ant venoms are a promising source of bioactive molecules, that integrating experimental and computational approaches accelerates their discovery in neglected taxa, and that the resulting economic value may constitute an argument for biodiversity conservation.