ArticleParasites & vectors2020
Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance.
Article in Parasites & vectors, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Zoonotic leishmaniasis in China: Current status and challenges to elimination.PLoS neglected tropical diseases · 2026Review
- Upregulation of PD-1/PD-L1 and downregulation of immune signaling pathways lead to more severe visceral leishmaniasis in undernutrition mice.Parasites & vectors · 2024Article
- Mutation Characteristics and Phylogenetic Analysis of FiveAnimals : an open access journal from MDPI · 2022Article
- Impact of Genetic Diversity and Genome Plasticity ofFrontiers in cellular and infection microbiology · 2022Review
- Screening Novel Vaccine Candidates forFrontiers in immunology · 2022Article
- Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony.Parasites & vectors · 2021Article
- Metabolite Biomarkers ofCells · 2021Article
- Drug-Induced Lipid Remodeling inMicroorganisms · 2021Article
- Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea?Frontiers in medicine · 2021Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundLeishmaniasis is a neglected tropical disease affecting millions of people worldwide. Emerging drug resistance of Leishmania species poses threaten to the effective control and elimination programme of this neglected tropical disease.
methodsIn this work, we conducted drug-resistance testing, whole genome resequencing and proteome profiling for a recently reported clinical isolate with supposed drug resistance (HCZ), and two reference sensitive strains (DD8 and 9044) of Leishmania donovani, to explore molecular mechanisms underlying drug resistance in this parasite.
resultsWith reference to DD8 and 9044 strains, HCZ isolate showed higher-level virulence and clear resistance to antimonials in promastigote culture, infected macrophages and animal experiment. Pairwise genomic comparisons revealed genetic variations (86 copy number variations, 271 frameshift mutations in protein-coding genes and two site mutations in non-coding genes) in HCZ isolate that were absent from the reference sensitive strains. Proteomic analysis indicated different protein expression between HCZ isolate and reference strains, including 69 exclusively detected proteins and 82 consistently down-/upregulated molecules in the HCZ isolate. Integrative analysis showed linkage of 12 genomic variations (gene duplication, insertion and deletion) and their protein expression changes in HCZ isolate, which might be associated with pathogenic and antimony-resistant phenotype. Functional annotation analyses further indicated that molecules involved in nucleotide-binding, fatty acid metabolism, oxidation-reduction and transport might play a role in host-parasite interaction and drug-resistance.
conclusionsThis comprehensive integrative work provided novel insights into the genetic basis underlying virulence and resistance, suggesting new aspects to be investigated for a better intervention against L. donovani and associated diseases.
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