Trypanothione synthetase confers growth, survival advantage and resistance to anti-protozoal drugs in Trypanosoma cruzi.
Amide Synthases
/ genetics
Animals
Antioxidants
/ metabolism
Antiprotozoal Agents
/ therapeutic use
Cell Proliferation
Cells, Cultured
Chagas Cardiomyopathy
/ drug therapy
Drug Resistance
Humans
Oxidation-Reduction
Oxidative Stress
Protozoan Proteins
/ genetics
Transgenes
/ genetics
Trypanosoma cruzi
/ physiology
Anti-parasite drugs
Chagas disease
Paullones
Small molecule inhibitors
Trypanosoma cruzi
Trypanothione synthetase
Journal
Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
21
05
2018
revised:
09
10
2018
accepted:
20
10
2018
pubmed:
26
10
2018
medline:
18
2
2020
entrez:
26
10
2018
Statut:
ppublish
Résumé
Chagas cardiomyopathy, caused by Trypanosoma cruzi infection, continues to be a neglected illness, and has a major impact on global health. The parasite undergoes several stages of morphological and biochemical changes during its life cycle, and utilizes an elaborated antioxidant network to overcome the oxidants barrier and establish infection in vector and mammalian hosts. Trypanothione synthetase (TryS) catalyzes the biosynthesis of glutathione-spermidine adduct trypanothione (T(SH) We utilized genetic overexpression (TryS TryS is essential for proliferation and survival of T. cruzi under normal and oxidant stress conditions, and provides an advantage to the parasite to develop resistance against currently used anti-trypanosomal drugs. TryS indispensability has been chemically validated with inhibitors that may be useful for drug combination therapy against Chagas disease.
Sections du résumé
BACKGROUND
Chagas cardiomyopathy, caused by Trypanosoma cruzi infection, continues to be a neglected illness, and has a major impact on global health. The parasite undergoes several stages of morphological and biochemical changes during its life cycle, and utilizes an elaborated antioxidant network to overcome the oxidants barrier and establish infection in vector and mammalian hosts. Trypanothione synthetase (TryS) catalyzes the biosynthesis of glutathione-spermidine adduct trypanothione (T(SH)
METHODS AND RESULTS
We utilized genetic overexpression (TryS
CONCLUSIONS
TryS is essential for proliferation and survival of T. cruzi under normal and oxidant stress conditions, and provides an advantage to the parasite to develop resistance against currently used anti-trypanosomal drugs. TryS indispensability has been chemically validated with inhibitors that may be useful for drug combination therapy against Chagas disease.
Identifiants
pubmed: 30359758
pii: S0891-5849(18)32247-0
doi: 10.1016/j.freeradbiomed.2018.10.436
pmc: PMC6331241
mid: NIHMS1511258
pii:
doi:
Substances chimiques
Antioxidants
0
Antiprotozoal Agents
0
Protozoan Proteins
0
Amide Synthases
EC 6.3.1.-
trypanothione synthetase
EC 6.3.1.9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23-34Subventions
Organisme : NIAID NIH HHS
ID : R01 AI054578
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136031
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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