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In comparison to the well-studied\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    , there is a major paucity of knowledge regarding the biology of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    . Here, we use a combination of omics technologies and novel genetic tools to characterise core metabolism in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    mammalian-infective bloodstream-form parasites, and test whether metabolic differences compared to\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    impact upon sensitivity to metabolic inhibition. Like the bloodstream stage of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    , glycolysis plays a major part in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    energy metabolism. However, the rate of glucose uptake is significantly lower in bloodstream stage\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    , with cells remaining viable when cultured in concentrations as low as 2 mM. Instead of pyruvate, the primary glycolytic endpoints are succinate, malate and acetate. Transcriptomics analysis showed higher levels of transcripts associated with the mitochondrial pyruvate dehydrogenase complex, acetate generation, and the glycosomal succinate shunt in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    , compared to\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    . Stable-isotope labelling of glucose enabled the comparison of carbon usage between\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    and\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    , highlighting differences in nucleotide and saturated fatty acid metabolism. To validate the metabolic similarities and differences, both species were treated with metabolic inhibitors, confirming that electron transport chain activity is not essential in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    . However, the parasite exhibits increased sensitivity to inhibition of mitochondrial pyruvate import, compared to\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    . Strikingly,\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    exhibited significant resistance to inhibitors of fatty acid synthesis, including a 780-fold higher EC\n                    <jats:sub>50<\/jats:sub>\n                    for the lipase and fatty acid synthase inhibitor Orlistat, compared to\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    . These data highlight that bloodstream form\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>congolense<\/jats:italic>\n                    diverges from\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    in key areas of metabolism, with several features that are intermediate between bloodstream- and insect-stage\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    . These results have implications for drug development, mechanisms of drug resistance and host-pathogen interactions.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009734","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T13:34:13Z","timestamp":1627306453000},"page":"e1009734","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-5898","authenticated-orcid":true,"given":"Pieter C.","family":"Steketee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4509-5045","authenticated-orcid":true,"given":"Emily 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