ArticleMolecular microbiology2019
Sterol methyltransferase is required for optimal mitochondrial function and virulence in Leishmania major.
Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 60 citations in OpenAlex.
- Functional Dissection ofToxins · 2026Article
- Role of ergosterol biosynthesis in growth, drug sensitivity, and host colonization of honey bee trypanosomatid parasite,FEMS microbes · 2026Article
- A Comparative Study of Common Anesthetics Propofol, Sevoflurane, Isoflurane and Ketamine on Lipid Membrane Fluidity.International journal of molecular sciences · 2025Article
- Synthesis and evaluation of nitrochromene derivatives as potential antileishmanial therapeutics through biological and computational studies.Scientific reports · 2025Article
- Targeting Leishmaniasis with Nitrovinyl Derivatives: Synthesis,Current medicinal chemistry · 2025Article
- Genome analyses of amphotericin B-susceptible and -resistant strains ofCurrent research in parasitology & vector-borne diseases · 2025Article
- N-substituted-4-(pyridin-4-ylalkyl)piperazine-1-carboxamides and related compounds as Leishmania CYP51 and CYP5122A1 inhibitors.Bioorganic & medicinal chemistry · 2024Article
- Molecular Characterization of Sterol C4-Methyl Oxidase inInternational journal of molecular sciences · 2024Article
- Article
- From classical approaches to new developments in genetic engineering of live attenuated vaccine against cutaneous leishmaniasis: potential and immunization.Frontiers in public health · 2024Review
- Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-AttenuatedMicroorganisms · 2023Review
- Zinc(II)-Sterol Hydrazone Complex as a Potent Anti-Pharmaceutics · 2023Article
- InhibitingPharmaceuticals (Basel, Switzerland) · 2023Article
- Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response.PLoS neglected tropical diseases · 2022Article
- In-Depth Quantitative Proteomics Characterization of In Vitro Selected Miltefosine Resistance inProteomes · 2022Article
- Simvastatin Resistance ofMicroorganisms · 2022Article
- Homology Modeling,Frontiers in cellular and infection microbiology · 2022Article
- Endogenous Sterol Synthesis Is Dispensable forFrontiers in microbiology · 2022Article
- Unravelling the myth surrounding sterol biosynthesis as plausible target for drug design against leishmaniasis.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021Review
- Metabolic flexibility in Trypanosoma cruzi amastigotes: implications for persistence and drug sensitivity.Current opinion in microbiology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Limited knowledge on the exact functions of ergostane-based sterols has hampered the application of sterol synthesis inhibitors against trypanosomatid parasites. Sterol methyltransferase (SMT) is directly involved in the synthesis of parasite-specific C24-methylated sterols, including ergosterol and 5-dehydroepisterol. While pharmacological studies hint at its potential as a drug target against trypanosomatids, direct evidence for the cellular function and essentiality of SMT is lacking. Here, we characterized the SMT knockout mutants and their complemented strains in Leishmania major, the causative agent for cutaneous leishmaniasis. Deletion of SMT alleles led to a complete loss of C24-methylated sterols, which were replaced by cholestane-based sterols. SMT-null mutants were fully viable and replicative in culture but showed increased sensitivity to sphingolipid synthesis inhibition. They were not particularly vulnerable to heat, acidic pH, nitrosative or oxidative stress, yet exhibited high mitochondrial membrane potential and increased superoxide generation indicating altered physiology of the mitochondria. Despite possessing high levels of GPI-anchored glycoconjugates, SMT-null mutants showed significantly attenuated virulence in mice. In total, our study reveals that the biosynthesis of ergostane-based sterols is crucial for the proper function of mitochondria and the proliferation of Leishmania parasites in mammals.
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