title: Targeted gene expression profiling in Leishmania braziliensis and Leishmania guyanensis parasites isolated from Brazilian patients with different antimonial treatment outcomes.
abstract: 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.
authors.affiliation: Laboratório de Pesquisa em Leishmaniose, Coleção de Leishmania do Instituto Oswaldo Cruz IOC, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Davi Coe
authors.initials: DC
authors.lastname: Torres
authors.forename: Vanessa
authors.initials: V
authors.lastname: Adaui
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ribeiro-Alves
authors.forename: Gustavo A S
authors.initials: GA
authors.lastname: Romero
authors.forename: Jorge
authors.initials: J
authors.lastname: Arévalo
authors.forename: Elisa
authors.initials: E
authors.lastname: Cupolillo
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
mesh_terms: D000818:Animals; D000965:Antimony / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D001938:Brazil; D004351:Drug Resistance / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007892:Leishmania braziliensis / Q000235:genetics* / Q000302:isolation & purification; D018334:Leishmania guyanensis / Q000235:genetics* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008536:Meglumine / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000627:therapeutic use; D010271:Parasites / Q000235:genetics / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony