The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids

Abstract

Trypanosoma brucei, as well as Trypanosoma cruzi and more than 20 species of the genus Leishmania, form a group of flagellated protists that threaten human health. These organisms are transmitted by insects that, together with mammals, are their natural hosts. This implies that during their life cycles each of them faces environments with different physical, chemical, biochemical, and biological characteristics. In this work we review how amino acids are obtained from such environments, how they are metabolized, and how they and some of their intermediate metabolites are used as a survival toolbox to cope with the different conditions in which these parasites should establish the infections in the insects and mammalian hosts.

Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains

“…PMM r was associated with changes in 2-hydroxy acid production from certain amino acids. In Leishmania, the transamination of amino acids to their corresponding 2-keto acids involves a broad-specificity aminotransferase that can use aromatic amino acids and a branched-chain amino acid, aminotransferase (BCAT), with a specificity for leucine, isoleucine, and valine (27). The 2-hydroxy-acid dehydrogenase(s) responsible for the reduction of the 2-keto acids to form lactates has not been identified.…”

Structure, Properties, and Function of Glycosomes in Trypanosoma cruzi

“…cruzi, like other dixenous trypanosomatid parasites, undergoes an elaborate life cycle involving extracellular replicative epimastigotes in the triatomine digestive tube, non-replicative extracellular metacyclic and bloodstream trypomastigotes in the insect and mammalian host, respectively, and replicative amastigotes intracellularly in the cytosol of the mammalian cells. The different developmental stages differ importantly in morphology, but also in metabolism to adapt to the large nutritional conditions encountered in the different niches (Maugeri et al, 2011;Barisón et al, 2017;Avila et al, 2018;Marchese et al, 2018;Mattos et al, 2019). Since glycosomes harbor many enzymes of intermediary metabolism as well as enzymes of other metabolic processes which are differentially expressed, glycosomal metabolism has to undergo reprogramming.…”

The Influence of Environmental Cues on the Development of Trypanosoma cruzi in Triatominae Vector

“…After several cycles of cell division, amastigotes differentiate into intracellular epimastigotes (Almeida- de-Faria et al, 1999) and then into trypomastigotes, which burst from infected cells into the extracellular environment. These parasites can infect neighboring cells or reach the bloodstream, where they can spread the infection to other tissues, or they can be ingested by a kissing bug during its bloodmeal, and the bug will then transmit the infection to other hosts (reviewed in Marchese et al, 2018). The classic description of the parasite's development in the digestive tract of the insect (Chagas, 1909;Dias, 1934), in which blood trypomastigotes differentiate into epimastigotes in the stomach and then multiply continuously in the intestine, reaching the rectum, where they differentiate into metacyclic trypomastigotes, was initially refuted by Brack.…”