ArticlePLoS neglected tropical diseases2022
Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response.
Article in PLoS neglected tropical diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Microneedle-based injection of Fungizone/Amphotericin B: an effective treatment for American cutaneous leishmaniasis in mice.Drug delivery · 2026Article
- Emerging evidence for a multitude of mechanisms and factors that determine amphotericin B resistance in pathogenic fungi.Cell surface (Amsterdam, Netherlands) · 2026Review
- Biological Effects of Novel Synthetic Guanidine Derivatives TargetingMolecules (Basel, Switzerland) · 2026Article
- Review on macrophage polarization during visceral leishmaniasis and impact of glycoprotein.Glycoconjugate journal · 2026Review
- Role of ergosterol biosynthesis in growth, drug sensitivity, and host colonization of honey bee trypanosomatid parasite,FEMS microbes · 2026Article
- Cutaneous and Mucocutaneous Leishmaniasis: Perspectives on Immunity, Virulence, and Treatment.Biomedicines · 2025Review
- Sialic Acid and Colchicine Functionalized Silica Nanoparticles: A Novel Approach to Leishmanicidal Selective Treatments.Biomedicines · 2025Article
- Scrutinized lipid utilization disrupts Amphotericin-B responsiveness in clinical isolates ofeLife · 2025Article
- Genomic characterization of Leishmania (V.) braziliensis associated with antimony therapeutic failure and variable in vitro tolerance to amphotericin B.Scientific reports · 2025Article
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Progress in antileishmanial drugs: Mechanisms, challenges, and prospects.PLoS neglected tropical diseases · 2025Review
- Genome analyses of amphotericin B-susceptible and -resistant strains ofCurrent research in parasitology & vector-borne diseases · 2025Article
- Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions.PLoS neglected tropical diseases · 2024Article
- Possibility of re-purposing antifungal drugs posaconazole & isavuconazole against promastigote form of Leishmania major.The Indian journal of medical research · 2024Article
- Combination Therapy and Phytochemical-Loaded Nanosytems for the Treatment of Neglected Tropical Diseases.Pharmaceutics · 2024Review
- Evaluation of theACS infectious diseases · 2024Article
- Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1.PLoS pathogens · 2024Article
- Amphotericin B resistance in Leishmania amazonensis: In vitro and in vivo characterization of a Brazilian clinical isolate.PLoS neglected tropical diseases · 2024Article
- Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads.Biomolecules · 2024Review
- Synthetic biology for combating leishmaniasis.Frontiers in microbiology · 2024Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Amphotericin B is increasingly used in treatment of leishmaniasis. Here, fourteen independent lines of Leishmania mexicana and one L. infantum line were selected for resistance to either amphotericin B or the related polyene antimicrobial, nystatin. Sterol profiling revealed that, in each resistant line, the predominant wild-type sterol, ergosta-5,7,24-trienol, was replaced by other sterol intermediates. Broadly, two different profiles emerged among the resistant lines. Whole genome sequencing then showed that these distinct profiles were due either to mutations in the sterol methyl transferase (C24SMT) gene locus or the sterol C5 desaturase (C5DS) gene. In three lines an additional deletion of the miltefosine transporter gene was found. Differences in sensitivity to amphotericin B were apparent, depending on whether cells were grown in HOMEM, supplemented with foetal bovine serum, or a serum free defined medium (DM). Metabolomic analysis after exposure to AmB showed that a large increase in glucose flux via the pentose phosphate pathway preceded cell death in cells sustained in HOMEM but not DM, indicating the oxidative stress was more significantly induced under HOMEM conditions. Several of the lines were tested for their ability to infect macrophages and replicate as amastigote forms, alongside their ability to establish infections in mice. While several AmB resistant lines showed reduced virulence, at least two lines displayed heightened virulence in mice whilst retaining their resistance phenotype, emphasising the risks of resistance emerging to this critical drug.
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