{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:05:48Z","timestamp":1792037148222,"version":"4.4.0"},"reference-count":83,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["Grant no. 53\/16\/2012-CMB\/BMS and 6\/9-7(188)2018-ECDII"],"award-info":[{"award-number":["Grant no. 53\/16\/2012-CMB\/BMS and 6\/9-7(188)2018-ECDII"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Current therapy for visceral leishmaniasis (VL), compromised by drug resistance, toxicity, and high cost, demands for more effective, safer, and low-cost drugs. Artemisinin has been found to be an effectual drug alternative in experimental models of leishmaniasis. Comparative genome and transcriptome analysis of in vitro-adapted artesunate-resistant (K133AS-R) and -sensitive wild-type (K133WT) Leishmania donovani parasites was carried out using next-generation sequencing and single-color DNA microarray technology, respectively, to identify genes and interlinked pathways contributing to drug resistance. Whole-genome sequence analysis of K133WT vs. K133AS-R parasites revealed substantial variation among the two and identified 240 single nucleotide polymorphisms (SNPs), 237 insertion deletions (InDels), 616 copy number variations (CNVs) (377 deletions and 239 duplications), and trisomy of chromosome 12 in K133AS-R parasites. Transcriptome analysis revealed differential expression of 208 genes (fold change \u2265 2) in K133AS-R parasites. Functional categorization and analysis of modulated genes of interlinked pathways pointed out plausible adaptations in K133AS-R parasites, such as (i) a dependency on lipid and amino acid metabolism for generating energy, (ii) reduced DNA and protein synthesis leading to parasites in the quiescence state, and (iii) active drug efflux. The upregulated expression of cathepsin-L like protease, amastin-like surface protein, and amino acid transporter and downregulated expression of the gene encoding ABCG2, pteridine receptor, adenylatecyclase-type receptor, phosphoaceylglucosamine mutase, and certain hypothetical proteins are concordant with genomic alterations suggesting their potential role in drug resistance. The study provided an understanding of the molecular basis linked to artemisinin resistance in Leishmania parasites, which may be advantageous for safeguarding this drug for future use.<\/jats:p>","DOI":"10.3390\/genes11111362","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T22:46:46Z","timestamp":1605653206000},"page":"1362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genomic and Transcriptomic Analysis for Identification of Genes and Interlinked Pathways Mediating Artemisinin Resistance in Leishmania donovani"],"prefix":"10.3390","volume":"11","author":[{"given":"Sushmita","family":"Ghosh","sequence":"first","affiliation":[{"name":"ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi 110029, India"},{"name":"JH-Institute of Molecular Medicine, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Verma","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8075-1431","authenticated-orcid":false,"given":"Vinay","family":"Kumar","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2459-5032","authenticated-orcid":false,"given":"Dibyabhaba","family":"Pradhan","sequence":"additional","affiliation":[{"name":"ICMR-AIIMS Computational Genomics Centre, Indian Council of Medical Research, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angamuthu","family":"Selvapandiyan","sequence":"additional","affiliation":[{"name":"JH-Institute of Molecular Medicine, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Salotra","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8094-4703","authenticated-orcid":false,"given":"Ruchi","family":"Singh","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis [seminar]","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alvar, J., V\u00e9lez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., and de Boer, M. 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