Drug resistance analysis by next generation sequencing in Leishmania.
The use of next generation sequencing has the power to expedite the identification of drug resistance determinants and biomarkers and was applied successfully to drug resistance studies in Leishmania. This allowed the identification of modulation in gene expression, gene dosage alterations, changes in chromosome copy numbers and single nucleotide polymorphisms that correlated with resistance in Leishmania strains derived from the laboratory and from the field. An impressive heterogeneity at the population level was also observed, individual clones within populations often differing in both genotypes and phenotypes, hence complicating the elucidation of resistance mechanisms. This review summarizes the most recent highlights that whole genome sequencing brought to our understanding of Leishmania drug resistance and likely new directions.
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
Philippe
P
Leprohon
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
Christopher
C
Fernandez-Prada
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
Élodie
É
Gazanion
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
Rubens
R
Monte-Neto
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, 2705 Laurier Blvd., Québec G1V 4G2, Canada.
Marc
M
Ouellette
D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004351:Drug Resistance; D014644:Genetic Variation; D007891:Leishmania / Q000187:drug effects* / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*
D000981:Antiprotozoal Agents
Aneuploidy; Drug resistance; Gene amplification; Genome; Leishmania; Next generation sequencing; Single nucleotide polymorphisms