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However, little is known about how different species of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    manipulate host metabolism. Here, we demonstrate that despite differences in their mechanisms for evading host immune responses,\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>amazonensis<\/jats:italic>\n                    and\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>braziliensis<\/jats:italic>\n                    induce comparable disruptions in key metabolic pathways. We found that infected macrophages exhibited an overall elevation in energy metabolism regardless of the parasite strain, evidenced by the elevation in glycolysis and oxygen consumption rates, along with increased proton leak and decreased ATP production. We also analyzed the effects of both\n                    <jats:italic>Leishmania<\/jats:italic>\n                    spp. strain infection on mitochondria function, further revealing that infected cells display heightened mitochondrial mass and membrane potential. To investigate the metabolic pathways required for\n                    <jats:italic>Leishmania<\/jats:italic>\n                    amastigotes to persist in BMDMs, we pre-treated cells with small molecule drugs that target major metabolic pathways, revealing that perturbations in several metabolic processes affected parasite survival in a strain-independent manner. Treatments with inhibitors of the oxidative phosphorylation and glycolysis substantially reduced parasite loads. Collectively, our findings suggest that\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>amazonensis<\/jats:italic>\n                    and\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>braziliensis<\/jats:italic>\n                    exploit host cell metabolic pathways similarly to survive in macrophages.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0012763","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T13:48:41Z","timestamp":1736257721000},"page":"e0012763","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacological inhibition of key metabolic pathways attenuates Leishmania spp infection in macrophages"],"prefix":"10.1371","volume":"19","author":[{"given":"Elaine Carvalho","family":"de Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Tib\u00farcio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Lago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9on","family":"de Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Nunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Gast\u00e3o","family":"Davanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana J\u00falia","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Vinagre","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Moth\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana B. 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