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In addition to high toxicity, these drugs have low healing efficacy, especially in the chronic phase of the disease. The existence of drug-resistant <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic> strains and the occurrence of cross-resistance between BZ and NFX have also been described. In this context, it is urgent to study the metabolism of these drugs in <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic>, to better understand the mechanisms of resistance. Prostaglandin F2\u03b1 synthase (PGFS) is an enzyme that has been correlated with parasite resistance to BZ, but the mechanism by which resistance occurs is still unclear. Our results show that the genome of the CL Brener clone of <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic>, contains five PGFS sequences and three potential pseudogenes. Using CRISPR\/Cas9 we generated knockout cell lines in which all PGFS sequences were disrupted, as shown by PCR and western blotting analyses. The PGFS deletion did not alter the growth of the parasites or their susceptibility to BZ and NFX when compared to wild-type (WT) parasites. Interestingly, NTR-1 transcripts were shown to be upregulated in \u0394PGFS mutants. Furthermore, the \u0394PGFS parasites were 1.6 to 1.7-fold less tolerant to oxidative stress generated by menadione, presented lower levels of lipid bodies than the control parasites during the stationary phase, and were less infective than control parasites.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010845","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:30:22Z","timestamp":1666200622000},"page":"e0010845","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi"],"prefix":"10.1371","volume":"16","author":[{"given":"Ana Maria Murta","family":"Santi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Martins","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Lu\u00eds","family":"Reis-Cunha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela de Assis","family":"Burle-Caldas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella Fernandes Martins","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula Alves","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela de Melo","family":"Resende","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniella Castanheira","family":"Bartholomeu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santuza Maria Ribeiro","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-2155","authenticated-orcid":true,"given":"Silvane Maria Fonseca","family":"Murta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"pntd.0010845.ref001","first-page":"161","article-title":"Nova especie morbida do homem produzida por um trypanozoma (trypanozoma Cruzi).","volume":"23","author":"C. 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