ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021
Mutations in an Aquaglyceroporin as a Proven Marker of Antimony Clinical Resistance in the Parasite Leishmania donovani.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Multi-drug tolerance in Leishmania persister-like cells.Communications biology · 2026Article
- Differential Susceptibility to Antimony in Strains and Clinical Isolates ofPathogens (Basel, Switzerland) · 2026Article
- Direct sequencing of Leishmania donovani from patients in Garissa County, Northern Kenya, reveals a newly emerging intra-specific hybrid genotype.PLoS neglected tropical diseases · 2026Article
- Genetic Manipulation Tools in Leishmania: From CRISPR/Cas9 to Vaccine Strategies for Disease Control.Acta parasitologica · 2025Review
- Interventions for Neglected Diseases Caused by Kinetoplastid Parasites: A One Health Approach to Drug Discovery, Development, and Deployment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- In Vitro Leishmanicidal Efficacy of Synthesized Arylidene Analogues of Glitazone.Drug development research · 2025Article
- Current trends in application of CRISPR/Cas9 in gene editing and diagnostics in Neglected tropical diseases (NTDs).Molecular biology reports · 2025Review
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Article
- Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites.Genome research · 2024Article
- Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.ACS omega · 2024Review
- Design, synthesis, electrochemistry and anti-trypanosomatid hit/lead identification of nitrofuranylazines.RSC medicinal chemistry · 2023Article
- Oligo targeting for profiling drug resistance mutations in the parasitic trypanosomatids.Nucleic acids research · 2022Article
- Exploring novel nitrofuranyl sulfonohydrazides as anti-Leishmania and anti-cancer agents: Synthesis, in vitro efficacy and hit identification.Chemical biology & drug design · 2022Article
- Synthesis, in vitro Antileishmanial Efficacy and Hit/Lead Identification of Nitrofurantoin-Triazole Hybrids.ChemMedChem · 2022Article
- 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
- Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony.Parasites & vectors · 2021Article
- Downregulation of FeSOD-A expression in Leishmania infantum alters trivalent antimony and miltefosine susceptibility.Parasites & vectors · 2021Article
- Perspectives From Systems Biology to Improve Knowledge ofFrontiers in cellular and infection microbiology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAntimonial drugs have long been the mainstay to treat visceral leishmaniasis. Their use has been discontinued in the Indian subcontinent because of drug resistance, but they are still clinically useful elsewhere. The goal of this study was to find markers of antimony resistance in Leishmania donovani clinical isolates and validate experimentally their role in resistance.
methodsThe genomes of sensitive and antimony-resistant clinical isolates were sequenced. The role of a specific gene in contributing to resistance was studied by CRISPR-Cas9-mediated gene editing and intracellular drug sensitivity assays.
resultsBoth gene copy number variations and single nucleotide variants were associated with antimony resistance. A homozygous insertion of 2 nucleotides was found in the gene coding for the aquaglyceroporin AQP1 in both resistant isolates. Restoring the wild-type AQP1 open reading frame re-sensitized the 2 independent resistant isolates to antimonials. Alternatively, editing the genome of a sensitive isolate by incorporating the 2-nucleotide insertion in its AQP1 gene led to antimony-resistant parasites.
conclusionsThrough genomic analysis and CRISPR-Cas9-mediated genome editing we have proven the role of the AQP1 mutations in antimony clinical resistance in L. donovani.
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