{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T15:36:36Z","timestamp":1759073796269,"version":"3.40.5"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Acanthamoeba<\/jats:italic> spp. cause a corneal infection, <jats:italic>Acanthamoeba<\/jats:italic> keratitis (AK), and a cerebral infection, granulomatous amoebic encephalitis (GAE). Though aggressive chemotherapy has been able to kill the active trophozoite form of <jats:italic>Acanthamoeba<\/jats:italic>, the encysted form of this parasite has remained problematic to resist physiological concentrations of drugs. The emergence of encysted amoeba into active trophozoite form poses a challenge to eradicate this parasite. <jats:italic>Acanthamoeba<\/jats:italic> trophozoites have active metabolic machinery that furnishes energy in the form of ATPs by subjecting carbohydrates and lipids to undergo pathways including glycolysis and beta\u2010oxidation of free fatty acids, respectively. However, very little is known about the metabolic preferences and dependencies of an encysted trophozoite on minerals or potential nutrients that it consumes to live in an encysted state. Here, we investigate the metabolic and nutrient preferences of the encysted trophozoite of <jats:italic>Acanthamoeba castellanii<\/jats:italic> and the possibility to target them by drugs that act on calcium ion dependencies of the encysted amoeba. The experimental assays, immunostaining coupled with bioinformatics tools show that the encysted <jats:italic>Acanthamoeba<\/jats:italic> uses diverse nutrient pathways to obtain energy in the quiescent encysted state. These findings highlight potential pathways that can be targeted in eradicating amoebae cysts successfully.<\/jats:p>","DOI":"10.1111\/cbdd.13755","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T18:17:48Z","timestamp":1593541068000},"page":"18-27","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["\u2018Targeting the feast of a sleeping beast\u2019: Nutrient and mineral dependencies of encysted <i>Acanthamoeba castellanii<\/i>"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0626-216X","authenticated-orcid":false,"given":"Abdul Mannan","family":"Baig","sequence":"first","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University  Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveed Ahmed","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biology, Chemistry and Environmental Sciences College of Arts and Sciences American University of Sharjah  Sharjah United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preet","family":"Katyara","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University  Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salima","family":"Lalani","sequence":"additional","affiliation":[{"name":"Department of Virus and Vaccine Research Biological and Biomedical Sciences  Bandar Sunway Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozeena","family":"Baig","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University  Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdia","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University  Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor","family":"Akbar","sequence":"additional","affiliation":[{"name":"Department of Biology, Chemistry and Environmental Sciences College of Arts and Sciences American University of Sharjah  Sharjah United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fizza","family":"Nazim","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University  Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8514-4518","authenticated-orcid":false,"given":"Areeba","family":"Khaleeq","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University  Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00299-13"},{"issue":"12","key":"e_1_2_7_3_1","first-page":"64","article-title":"Eukaryotic cell encystation and cancer cell dormancy: Is a greater devil veiled in the details of a lesser evil?","volume":"2015","author":"Baig A. M.","year":"2015","journal-title":"Cancer Biol Med"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871526517666170622075154"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2016.01.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050691f"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2009.04.009"},{"issue":"3","key":"e_1_2_7_8_1","first-page":"1371","article-title":"Amiodarone inhibits the mitochondrial beta\u2010oxidation of fatty acids and produces microvesicular steatosis of the liver in mice","volume":"255","author":"Fromenty B.","year":"1990","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2010.02161.x"},{"volume-title":"Acanathamoeba castellanii, metabolic pathways","year":"2020","author":"KEGG Pathways","key":"e_1_2_7_10_1"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2006.00023.x"},{"volume-title":"Goodman & Gilman\u2019s \u2018The Pharmacological basis of Therapeutics\u2019","year":"2011","author":"Laurence L. B.","key":"e_1_2_7_12_1"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2014.03.026"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913660107"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.16.2.273-307.2003"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01426-12"},{"issue":"4","key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1016\/S0021-9258(18)52237-7","article-title":"Muscle glycogenolysis. Regulation of the cyclic. interconversion of phosphorylase a and phosphorylase b","volume":"266","author":"Meinke M. H.","year":"1991","journal-title":"Journal of Biological Chemistry"},{"volume-title":"Lehninger principles of biochemistryLehninger Principles of Biochemistry (6th Edition)","year":"2000","author":"Nelson D. L.","key":"e_1_2_7_18_1"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1139\/m73-180"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2007.00232.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05734-x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920009787522133"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcbdd.13755","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13755","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.13755","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13755","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T13:47:02Z","timestamp":1693748822000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.13755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,12]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/cbdd.13755"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.13755","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"type":"print","value":"1747-0277"},{"type":"electronic","value":"1747-0285"}],"subject":[],"published":{"date-parts":[[2020,8,12]]},"assertion":[{"value":"2019-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}