Endosymbiosis in trypanosomatids: the bacterium regulates the intermediate and oxidative metabolism of the host cell

ABSTRACT Endosymbiosis in trypanosomatids involves a mutualistic association between a symbiotic bacterium and a host protozoan and represents an excellent model for studying metabolic coevolution and the origin of organelles. This work investigated the influence of the symbiont on the metabolism of Angomonas deanei by comparing wild-type and aposymbiotic strains under different nutritional conditions. The presence of the symbiont enhanced cell proliferation in the medium containing a single carbon source and increased O₂ consumption. Wild-type cells utilized oxidative phosphorylation to produce ATP, whereas aposymbiotic cells relied on substrate-level glycolysis, resulting in the excretion of greater amounts of fermentative products, such as acetate, succinate, and ethanol. Proteomic analysis revealed an increased expression of glycolytic and fermentative enzymes by the aposymbiotic strain and oxidative phosphorylation enzymes by symbiont-harboring cells. These findings highlight the role of the symbiotic bacterium in optimizing host metabolism and provide insights into the evolution of parasitism in trypanosomatids when A. deanei is compared with pathogenic species. IMPORTANCE This work provides groundbreaking insights into the metabolic and evolutionary dynamics of endosymbiosis, a topic of central importance to cellular evolution. Angomonas deanei, a trypanosomatid species, has become a paradigm for investigating the evolution of eukaryotic cells and the origin of organelles through endosymbiosis. Harbored in the cytoplasm of this protozoan, the symbiont engages in intricate metabolic exchanges, offering a time window to analyze the processes and evolutionary history that underlie the establishment of permanent endosymbiotic relationships. By employing a multidisciplinary approach, we have uncovered how the symbiotic bacterium regulates the oxidative metabolism of the trypanosomatid, integrating glucose catabolism and optimizing energy production. Our discoveries have broad implications for understanding the metabolic integration of organelles, such as mitochondria and glycosomes, with the bacterial endosymbiont. Beyond unravelling the complexities of metabolic adaptations during symbiosis, our work may contribute to the general understanding of the evolutionary dynamics of parasitism within the Trypanosomatidae family.