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The parasite has developed various mechanisms to get through its intricate life cycle and adapt to different evolutionary phases. <jats:italic>T. cruzi<\/jats:italic> proliferates in the insect vector's digestive tract as an epimastigote form, encountering fluctuating nutrient availability and oxidative stress caused by the digestion of red blood cells from the mammalian host blood meal. To unravel how the parasite's metabolism adapts to these changing conditions, we conducted an analysis of the chemical species present in epimastigote forms. This involved comparing cultured parasites with those subjected to nutritional deficiency or oxidative stress using untargeted metabolomics. We looked at 21 samples: seven biological copies of parasites that were actively growing, seven samples that were put in a medium without nutrients for 3\u2009h, and seven samples that were treated with glucose oxidase for 30\u2009min to make H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> continuously. Importantly, in all conditions, parasite viability was maintained when the samples were collected. Upon nutrient removal, we observed a substantial decrease in amino acids and carbohydrate metabolites, accompanied by the accumulation of fatty acids and steroids, with the predominance of inositol and sphingolipid metabolism, along with a simultaneous decrease in the levels of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. In the presence of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, a significant rise in components of the pentose pathway and specific amino acids such as methionine and serine occurred, along with pathways related to an increase in antioxidant species metabolism such as ribulose 5\u2010phosphate and glyceric acid. Conversely, fatty acid and steroid levels decrease. We found no common increase in metabolites or lipids. In contrast, eight species (succinic acid, glutamic acid, valine, 2\u2010hydroxyisocaproic acid, alanine, indolelactic acid, proline, and lanosterol) were consumed under both stresses. These findings underscore the rapid and distinct enrichment responses in amino acids, lipids, and carbohydrates required to cope with each different environmental condition. We concluded that <jats:italic>T. cruzi<\/jats:italic> presents a flexible metabolism that rapidly adapts to variable changes in the environment.<\/jats:p>","DOI":"10.1111\/mmi.15279","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T15:30:13Z","timestamp":1717083013000},"page":"704-719","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The effect of nutritional and oxidative stress on the metabolome of <i>Trypanosoma cruzi<\/i>"],"prefix":"10.1111","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-7810","authenticated-orcid":false,"given":"Michel Augusto","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-6719","authenticated-orcid":false,"given":"Mario Augusto","family":"Izidoro","sequence":"additional","affiliation":[{"name":"Hospital S\u00e3o Paulo  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4905-3982","authenticated-orcid":false,"given":"Mirella","family":"Aric\u00f3","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-2822","authenticated-orcid":false,"given":"Luiz","family":"Juliano","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9353-8480","authenticated-orcid":false,"given":"Sergio","family":"Schenkman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.45.27244"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10292-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.05.003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.26434\/chemrxiv-2021-l64kg"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.31.18387"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.105.4.1101"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20200142"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvac061"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-016-9665-9"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.778522"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(81)90049-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2020.111324"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004792"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.03.017"},{"key":"e_1_2_9_17_1","first-page":"93","article-title":"Growth and differentiation in Trypanosoma cruzi. 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