{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:05:47Z","timestamp":1792037147120,"version":"4.4.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:00:00Z","timestamp":1598054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FND167283"],"award-info":[{"award-number":["FND167283"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Antimonial drugs have long been the mainstay to treat visceral leishmaniasis. Their use has been discontinued in the Indian subcontinent because of drug resistance, but they are still clinically useful elsewhere. The goal of this study was to find markers of antimony resistance in Leishmania donovani clinical isolates and validate experimentally their role in resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The genomes of sensitive and antimony-resistant clinical isolates were sequenced. The role of a specific gene in contributing to resistance was studied by CRISPR-Cas9\u2013mediated gene editing and intracellular drug sensitivity assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Both gene copy number variations and single nucleotide variants were associated with antimony resistance. A homozygous insertion of 2 nucleotides was found in the gene coding for the aquaglyceroporin AQP1 in both resistant isolates. Restoring the wild-type AQP1 open reading frame re-sensitized the 2 independent resistant isolates to antimonials. Alternatively, editing the genome of a sensitive isolate by incorporating the 2-nucleotide insertion in its AQP1 gene led to antimony-resistant parasites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Through genomic analysis and CRISPR-Cas9\u2013mediated genome editing we have proven the role of the AQP1 mutations in antimony clinical resistance in L. donovani.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa1236","type":"journal-article","created":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T19:31:29Z","timestamp":1597692689000},"page":"e526-e532","source":"Crossref","is-referenced-by-count":46,"title":["Mutations in an Aquaglyceroporin as a Proven Marker of Antimony Clinical Resistance in the Parasite <i>Leishmania donovani<\/i>"],"prefix":"10.1093","volume":"72","author":[{"given":"Jade-Eva","family":"Potvin","sequence":"first","affiliation":[{"name":"Division of Infectious Disease and Immunity, CHU de Quebec Research Center and Department of Microbiology, Infectious Disease, and Immunology, University Laval, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Leprohon","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and Immunity, CHU de Quebec Research Center and Department of Microbiology, Infectious Disease, and Immunology, University Laval, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Queffeulou","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and Immunity, CHU de Quebec Research Center and Department of Microbiology, Infectious Disease, and Immunology, University Laval, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ouellette","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and Immunity, CHU de Quebec Research Center and Department of Microbiology, Infectious Disease, and Immunology, University Laval, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,22]]},"reference":[{"key":"2021051810395009200_CIT0001","doi-asserted-by":"crossref","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PLoS 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