ArticleGenome biology2008
Modulation of gene expression in drug resistant Leishmania is associated with gene amplification, gene deletion and chromosome aneuploidy.
Article in Genome biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 172 citations in OpenAlex.
- Genome-wide mapping of replication stress response factors reveals the management of polycistronic transcription, replication initiation, and responses to replication stress in Leishmania.Nucleic acids research · 2026Article
- The atypical dual-specificity protein phosphatase (DUSP)/kinatase of Leishmania infantum modulates infectivity, oxidative stress response and antimonial resistance.PLoS neglected tropical diseases · 2026Article
- Combinatorial effects of multiple genes contribute to beneficial aneuploidy phenotypes.EMBO reports · 2026Article
- PvDBP gene amplification is associated with functional immune evasion by Plasmodium vivax in vivo.Research square · 2026Article
- Trypanosomatid parasites, translational research in a One Health, One World environment.Frontiers in chemistry · 2026Review
- Cutaneous and Mucocutaneous Leishmaniasis: Perspectives on Immunity, Virulence, and Treatment.Biomedicines · 2025Review
- Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area.Parasites & vectors · 2025Article
- Upregulation of antioxidant genes in antimony-resistant Leishmania tropica clinical isolates.Molecular biology reports · 2025Article
- R-loops acted on by RNase H1 influence DNA replication timing and genome stability in Leishmania.Nature communications · 2025Article
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Understanding the genetic complexity of Leishmania infantum in the Americas: a focus on 3'NT/NU gene deletion.Memorias do Instituto Oswaldo Cruz · 2025Review
- Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions.PLoS neglected tropical diseases · 2024Article
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Antiprotozoal peptide prediction using machine learning with effective feature selection techniques.Heliyon · 2024Article
- Potential selection of antimony and methotrexate cross-resistance in Leishmania infantum circulating strains.PLoS neglected tropical diseases · 2024Article
- Genomic analysis of Leishmania turanica strains from different regions of Central Asia.PLoS neglected tropical diseases · 2023Article
- Life in plastic, it's fantastic! HowFrontiers in cellular and infection microbiology · 2023Review
- The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective.Frontiers in cellular and infection microbiology · 2023Review
- Self-Hybridization in Leishmania major.mBio · 2022Article
- Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response.PLoS neglected tropical diseases · 2022Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrug resistance can be complex, and several mutations responsible for it can co-exist in a resistant cell. Transcriptional profiling is ideally suited for studying complex resistance genotypes and has the potential to lead to novel discoveries. We generated full genome 70-mer oligonucleotide microarrays for all protein coding genes of the human protozoan parasites Leishmania major and Leishmania infantum. These arrays were used to monitor gene expression in methotrexate resistant parasites.
resultsLeishmania is a eukaryotic organism with minimal control at the level of transcription initiation and few genes were differentially expressed without concomitant changes in DNA copy number. One exception was found in Leishmania major, where the expression of whole chromosomes was down-regulated. The microarrays highlighted several mechanisms by which the copy number of genes involved in resistance was altered; these include gene deletion, formation of extrachromosomal circular or linear amplicons, and the presence of supernumerary chromosomes. In the case of gene deletion or gene amplification, the rearrangements have occurred at the sites of repeated (direct or inverted) sequences. These repeats appear highly conserved in both species to facilitate the amplification of key genes during environmental changes. When direct or inverted repeats are absent in the vicinity of a gene conferring a selective advantage, Leishmania will resort to supernumerary chromosomes to increase the levels of a gene product.
conclusionAneuploidy has been suggested as an important cause of drug resistance in several organisms and additional studies should reveal the potential importance of this phenomenon in drug resistance in Leishmania.
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