Exploring Bacteria from Extreme Environments in Chilean Patagonia for Antitrypanosomal Metabolites

Abstract Extreme environments are recognized as valuable reservoirs of microbial diversity and chemical novelty. Adapted to harsh environmental conditions, bacteria isolated from extreme environments exhibit unique biosynthetic capabilities associated with the production of structurally diverse bioactive metabolites. Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, remains one of the most important neglected tropical diseases, affecting approximately eight million people worldwide. Current chemotherapy relies on only two drugs, benznidazole and nifurtimox, both associated with toxicity and therapeutic limitations. The search for new antitrypanosomal agents has therefore intensified, directing attention to underexplored microbial resources such as bacteria isolated from extreme environments, which are known for their remarkable biosynthetic potential and chemical diversity. In this context, the present study investigated the anti-T. cruzi potential of extracts obtained from sediment-associated microbial communities from the Magallanes Region of Chilean Patagonia. By using 16S rRNA sequencing, seven bacterial isolates from extreme environments were identified as belonging to the genus Roseovarius spp., Loktanella spp., Pseudarthrobacter spp., Pseudomonas spp., Psychroflexus spp., and Cyclobacterium spp. The antiparasitic activity of the extracts was determined in trypomastigotes, resulting in potent IC50 values ranging from 2 to 18 μg/mL. Bioactivity-guided fractionation of the Cyclobacterium plantarum extract led to the putative identification of VAS8, a phosphatidylethanolamine derivative, as its active constituent. VAS8 exhibited activity against both trypomastigote (IC50 = 49 μM) and intracellular amastigote (IC50 = 19 μM) forms of T. cruzi, while showing no significant cytotoxicity toward mammalian host cells (CC50 > 150 μM). Spectrofluorimetric and fluorescence microscopy studies using SYTOX Green demonstrated a time/concentration-dependent permeabilization of the plasma membrane after VAS8 incubation with trypomastigotes. These findings highlight bacteria isolated from extreme environments as a promising source of antitrypanosomal metabolites and phosphatidylethanolamines as attractive scaffolds for the development of new therapies against Chagas disease.