Laboratório de Pesquisa em Leishmaniose, Coleção de Leishmania do Instituto Oswaldo Cruz IOC, Fiocruz, Rio de Janeiro, Brazil.
Infect Genet Evol. 2010 Aug;10(6):727-33. doi: 10.1016/j.meegid.2010.05.006. Epub 2010 May 15.
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, gamma-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.
在巴西，皮肤利什曼病是一个严重的公共卫生问题，化疗是该病临床管理的重要手段。然而，治疗效果存在差异，这种现象可能是由于宿主和寄生虫（如药物耐药性）因素所致。为了更好地了解寄生虫因素对此现象的可能贡献，我们对 12 株来自不同锑类药物治疗结果的巴西利什曼原虫（LB）和 25 株圭亚那利什曼原虫（LG）分离株进行了特征描述。对于每个分离株，均在对数晚期和静止期分别进行双份原代培养并收获。采用实时定量 PCR 评估了六个编码参与锑代谢的蛋白（AQP1、MRPA、GSH1、GSH2、TRYR 和 TDR1）的基因的 RNA 表达谱。将分子数据与临床表型进行比较。在 LB 中，我们未发现不同治疗结果患者来源的分离株之间所研究基因的表达水平存在统计学差异。在 LG 中，无论生长曲线阶段如何，治疗失败的分离株中 GSH1（编码γ-谷氨酰半胱氨酸合成酶，γ-GCS）的表达均过度上调。这一发现揭示了巴西 LG 引起的皮肤利什曼病的原代培养物表达曲线对预后的预测潜力。
