Ascorbate peroxidase overexpression protects Leishmania braziliensis against trivalent antimony effects
Mem. Inst. Oswaldo Cruz
; 113(12): e180377, 2018. graf
Article
em En
| LILACS
| ID: biblio-1040587
Biblioteca responsável:
BR1.1
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Leishmania braziliensis
/
Ascorbato Peroxidases
/
Antimônio
/
Antiprotozoários
País/Região como assunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
MEDICINA TROPICAL
/
PARASITOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Brasil