Drug resistance analysis by next generation sequencing in Leishmania

•WGS revealed the complexity of resistance which is often polyclonal in Leishmania.•An impressive variation in chromosome copy numbers exist between Leishmania species.•The genotype heterogeneity complicates the analysis of resistance in field isolates.

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.

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