ArticleInternational journal for parasitology. Drugs and drug resistance2018
Resistance of Leishmania infantum to allopurinol is associated with chromosome and gene copy number variations including decrease in the S-adenosylmethionine synthetase (METK) gene copy number.
Article in International journal for parasitology. Drugs and drug resistance, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Direct quantitative PCR detects genetic biomarkers of antileishmanial drug resistance in clinical samples from dogs with leishmaniosis.BMC veterinary research · 2026Article
- Updated Canine Leishmaniosis Working Group recommendations for leishmaniosis in dogs: Q&A on clinical management.Parasites & vectors · 2026Review
- Copy numbers of theCurrent research in parasitology & vector-borne diseases · 2026Article
- Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area.Parasites & vectors · 2025Article
- Unveiling prognostic indicators in canine leishmaniosis: two decades of evidence.Parasites & vectors · 2025Article
- Evidence for in vivo resistance against allopurinol in a dog infected with Leishmania infantum by reduction in copy numbers of the S-adenosylmethionine synthetase (METK) gene.Parasites & vectors · 2024Article
- New immunomodulatory treatment protocol for canine leishmaniosis reduces parasitemia and proteinuria.PLoS neglected tropical diseases · 2024Article
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Targeting trypanosomes: how chemogenomics and artificial intelligence can guide drug discovery.Biochemical Society transactions · 2023Review
- Identification ofMicroorganisms · 2022Article
- Canine Leishmaniasis: Update on Epidemiology, Diagnosis, Treatment, and Prevention.Veterinary sciences · 2022Review
- Nutritional Modulation of the Immune Response Mediated by Nucleotides in Canine Leishmaniosis.Microorganisms · 2021Review
- Revisiting the heterogeneous global genomic population structure ofMicrobial genomics · 2021Article
- The Effects of Polyhexamethylene Biguanide (PHMB) and TLR Agonists Alone or as Polyplex Nanoparticles againstVeterinary sciences · 2020Article
- Nuclear and mitochondrial genome sequencing of North-AfricanMicrobial genomics · 2020Article
- Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance.Antimicrobial agents and chemotherapy · 2020Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Genomewide Analysis of Mode of Action of themSystems · 2019Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania infantum is one of the causative agents of visceral leishmaniasis (VL), a widespread, life-threatening disease. This parasite is responsible for the majority of human VL cases in Brazil, the Middle East, China, Central Asia and the Mediterranean basin. Its main reservoir are domestic dogs which, similar to human patients, may develop severe visceral disease and die if not treated. The drug allopurinol is used for the long-term maintenance of dogs with canine leishmaniasis. Following our report of allopurinol resistance in treated relapsed dogs, we investigated the mechanisms and markers of resistance to this drug. Whole genome sequencing (WGS) of clinical resistant and susceptible strains, and laboratory induced resistant parasites, was carried out in order to detect genetic changes associated with resistance. Significant gene copy number variation (CNV) was found between resistant and susceptible isolates at several loci, including a locus on chromosome 30 containing the genes LinJ.30.3550 through LinJ.30.3580. A reduction in copy number for LinJ.30.3560, encoding the S-adenosylmethionine synthetase (METK) gene, was found in two resistant clinical isolates and four induced resistant clonal strains. Using quantitative real time PCR, this reduction in METK copy number was also found in three additional resistant clinical isolates. Furthermore, inhibition of S-adenosylmethionine synthetase encoded by the METK gene in allopurinol susceptible strains resulted in increased allopurinol resistance, confirming its role in resistance to allopurinol. In conclusion, this study identified genetic changes associated with L. infantum resistance to allopurinol and the reduction in METK copy number identified may serve as a marker for resistance in dogs, and reduced protein activity correlated with increased allopurinol resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.