Ascorbate peroxidase overexpression protects Leishmania braziliensis against trivalent antimony effects
Mem. Inst. Oswaldo Cruz
;
113(12): e180377, 2018. graf
Article
in English
| LILACS
| ID: biblio-1040587
ABSTRACT
Ascorbate peroxidase (APX) is a redox enzyme of the trypanothione pathway that converts hydrogen peroxide (H2O2) into water molecules. In the present study, the APX gene was overexpressed in Leishmania braziliensis to investigate its contribution to the trivalent antimony (SbIII)-resistance phenotype. Western blot results demonstrated that APX-overexpressing parasites had higher APX protein levels in comparison with the wild-type line (LbWTS). APX-overexpressing clones showed an 8-fold increase in the antimony-resistance index over the parental line. In addition, our results indicated that these clones were approximately 1.8-fold more tolerant to H2O2 than the LbWTS line, suggesting that the APX enzyme plays an important role in the defence against oxidative stress. Susceptibility tests revealed that APX-overexpressing L. braziliensis lines were more resistant to isoniazid, an antibacterial agent that interacts with APX. Interestingly, this compound enhanced the anti-leishmanial SbIII effect, indicating that this combination represents a good strategy for leishmaniasis chemotherapy. Our data demonstrate that APX enzyme is involved in the development of L. braziliensis antimony-resistance phenotype and may be an attractive therapeutic target in the design of new strategies for leishmaniasis treatment.
Full text:
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Index:
LILACS (Americas)
Main subject:
Leishmania braziliensis
/
Ascorbate Peroxidases
/
Antimony
/
Antiprotozoal Agents
Country/Region as subject:
South America
/
Brazil
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2018
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Fundação Oswaldo Cruz-Fiocruz/BR
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