ArticlePLoS neglected tropical diseases2015
Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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46 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Leishmania spp. genetic factors associated with cutaneous leishmaniasis antimony pentavalent drug resistance: a systematic review.Memorias do Instituto Oswaldo Cruz · 2024Pooled it
- Glycosomal Aquaglyceroporin 1 dual role in iron homeostasis and antimony susceptibility in Leishmania amazonensis.PLoS neglected tropical diseases · 2026Article
- Resequencing and De Novo Assembly ofPathogens (Basel, Switzerland) · 2026Article
- Cutaneous and Mucocutaneous Leishmaniasis: Perspectives on Immunity, Virulence, and Treatment.Biomedicines · 2025Review
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.ACS omega · 2024Review
- Antimony resistance and gene expression inParasitology · 2024Review
- The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress.EMBO reports · 2023Article
- Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies.PLoS pathogens · 2023Article
- The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective.Frontiers in cellular and infection microbiology · 2023Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Impact of Genetic Diversity and Genome Plasticity ofFrontiers in cellular and infection microbiology · 2022Review
- Exploring direct and indirect targets of current antileishmanial drugs using a novel thermal proteomics profiling approach.Frontiers in cellular and infection microbiology · 2022Article
- Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication.Parasites & vectors · 2021Article
- Three different mutations in the DNA topoisomerase 1B in Leishmania infantum contribute to resistance to antitumor drug topotecan.Parasites & vectors · 2021Article
- Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony.Parasites & vectors · 2021Article
- Mutations in an Aquaglyceroporin as a Proven Marker of Antimony Clinical Resistance in the Parasite Leishmania donovani.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Nuclear and mitochondrial genome sequencing of North-AfricanMicrobial genomics · 2020Article
- MRPA-independent mechanisms of antimony resistance in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2020Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAntimony resistance complicates the treatment of infections caused by the parasite Leishmania. METHODOLOGY/PRINCIPAL
findingsUsing next generation sequencing, we sequenced the genome of four independent Leishmania guyanensis antimony-resistant (SbR) mutants and found different chromosomal alterations including aneuploidy, intrachromosomal gene amplification and gene deletion. A segment covering 30 genes on chromosome 19 was amplified intrachromosomally in three of the four mutants. The gene coding for the multidrug resistance associated protein A involved in antimony resistance was also amplified in the four mutants, most likely through chromosomal translocation. All mutants also displayed a reduced accumulation of antimony mainly due to genomic alterations at the level of the subtelomeric region of chromosome 31 harboring the gene coding for the aquaglyceroporin 1 (LgAQP1). Resistance involved the loss of LgAQP1 through subtelomeric deletions in three mutants. Interestingly, the fourth mutant harbored a single G133D point mutation in LgAQP1 whose role in resistance was functionality confirmed through drug sensitivity and antimony accumulation assays. In contrast to the Leishmania subspecies that resort to extrachromosomal amplification, the Viannia strains studied here used intrachromosomal amplification and locus deletion. CONCLUSIONS/SIGNIFICANCE: This is the first report of a naturally occurred point mutation in AQP1 in antimony resistant parasites.
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