Targeted gene expression profiling in **Leishmania braziliensis** and **Leishmania guyanensis** parasites isolated from Brazilian patients with different antimonial treatment outcomesTargeted gene expression profiling in **Leishmania braziliensis** and **Leishmania guyanensis** parasites isolated from Brazilian patients with different antimonial treatment outcomes
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Department of Biomedical Sciences - other
Department of Biomedical Sciences
Infection, genetics and evolution. - Amsterdam
10(2010):6, p. 727-733
University of Antwerp
In Brazil, cutaneous leishmaniasis represents a serious public health problem, and chemotherapy is an important element of the clinical management of this disease. However, treatment efficacy is variable, a phenomenon that might be due to host and parasite (e.g., drug resistance) factors. To better understand the possible contribution of parasite factors to this phenomenon, we characterised 12 Leishmania braziliensis (LB) and 25 Leishmania guyanensis (LG) isolates collected from patients experiencing different antimonial treatment outcomes. For each isolate, promastigote cultures were grown in duplicate and were harvested at the late-log and stationary phases of growth. The RNA expression profiles of six genes encoding proteins with roles in antimony metabolism (AQP1, MRPA, GSH1, GSH2, TRYR and TDR1) were assessed by means of real-time quantitative PCR. Molecular data were compared to the clinical phenotypes. Within LB, we did not find statistically significant differences in the expression levels of the examined genes among isolates from patients with different treatment outcomes. In LG, GSH1 (encoding gamma-glutamylcysteine synthetase, γ-GCS) was overexpressed in therapeutic failure isolates regardless of the growth curve phase. This finding reveals the predictive potential of promastigote expression curves for the prognosis of cutaneous leishmaniasis caused by LG in Brazil.