In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 16, No. 10 ( 2022-10-19), p. e0010845-
Abstract:
Chagas disease, caused by the protozoan Trypanosoma cruzi , is a serious chronic parasitic disease, currently treated with Nifurtimox (NFX) and Benznidazole (BZ). In addition to high toxicity, these drugs have low healing efficacy, especially in the chronic phase of the disease. The existence of drug-resistant T . cruzi 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 T . cruzi , to better understand the mechanisms of resistance. Prostaglandin F2α 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 T . cruzi , 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 ΔPGFS mutants. Furthermore, the ΔPGFS 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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0010845
DOI:
10.1371/journal.pntd.0010845.g001
DOI:
10.1371/journal.pntd.0010845.g002
DOI:
10.1371/journal.pntd.0010845.g003
DOI:
10.1371/journal.pntd.0010845.g004
DOI:
10.1371/journal.pntd.0010845.g005
DOI:
10.1371/journal.pntd.0010845.g006
DOI:
10.1371/journal.pntd.0010845.s001
DOI:
10.1371/journal.pntd.0010845.s002
DOI:
10.1371/journal.pntd.0010845.s003
DOI:
10.1371/journal.pntd.0010845.s004
DOI:
10.1371/journal.pntd.0010845.s005
DOI:
10.1371/journal.pntd.0010845.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2429704-5
Bookmarklink