Unresponsiveness to meglumine antimoniate in anthroponotic cutaneous leishmaniasis field isolates: analysis of resistance biomarkers by gene expression profiling.
Trop Med Int Health
; 23(6): 622-633, 2018 06.
Article
en En
| MEDLINE
| ID: mdl-29709098
ABSTRACT
BACKGROUND:
Resistance to antimonials is a fundamental determinant of treatment failure in anthroponotic cutaneous leishmaniasis (ACL). Detection of reliable molecular markers to distinguish unresponsive and responsive parasites is critical for consolidating strategies to monitor drug efficacy.METHODS:
We analysed the expression of five major antimony resistance-associated genes that is aquaglyceroporin1 (AQP1), γ-glutamylcysteine synthetase (γ-GCS), multidrug resistance protein A (MRPA), trypanothione reductase (TR) and thiol-dependent reductase 1 (TDR1), in unresponsive and responsive Leishmania tropica field isolates by quantitative real-time PCR in comparison with sensitive and resistant reference strains.RESULTS:
Gene expression analysis showed the down-regulation of AQP1, γ-GCS and TDR1 by a factor of 1.9, 1.7 and 3.55, respectively, in unresponsive isolates vs. responsive ones. The average RNA expression level of MRPA increased by a factor of 1.9 in the unresponsive group. Isolates exhibited a strong positive linear correlation between gene expression of AQP1 and γ-GCS. A negative correlation between the AQP1 and γ-GCS expression level and lesion duration in responsive patients indicated the potential role in diagnosing drug-unresponsive parasites in endemic areas of ACL.CONCLUSION:
In cases of inconclusive outcomes of resistance tests in clinical isolates, expression analysis of a set of influential genes can be beneficial to identify distinctive biomarkers between antimony-unresponsive and responsive parasites.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leishmania tropica
/
Leishmaniasis Cutánea
/
Antimoniato de Meglumina
/
Antiprotozoarios
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Animals
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Trop Med Int Health
Asunto de la revista:
MEDICINA TROPICAL
/
SAUDE PUBLICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Irán