{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:32:04Z","timestamp":1789810324844,"version":"4.0.1"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["UID 87903"],"award-info":[{"award-number":["UID 87903"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells.\n            <jats:italic>In vitro<\/jats:italic>\n            susceptibility tests, including a checkerboard assay, were performed to assess the response of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus neoformans<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus gattii<\/jats:named-content>\n            to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus<\/jats:named-content>\n            drugs.\n          <\/jats:p>","DOI":"10.1128\/aac.02810-15","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T03:18:44Z","timestamp":1464751124000},"page":"4799-4808","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs"],"prefix":"10.1128","volume":"60","author":[{"given":"Adepemi O.","family":"Ogundeji","sequence":"first","affiliation":[{"name":"Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina H.","family":"Pohl","sequence":"additional","affiliation":[{"name":"Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olihile M.","family":"Sebolai","sequence":"additional","affiliation":[{"name":"Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2006.00113.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/B978-0-444-52149-1.00002-1","volume-title":"The yeasts, a taxonomic study","author":"Cooper CR","year":"2011","unstructured":"Cooper CR, Jr. 2011. Yeasts pathogenic to humans, p 9\u201320. In Kurtzman CP, Fell JW, Boekhout T (ed), The yeasts, a taxonomic study, 5th ed. Elsevier Sciences B.V., Amsterdam, Netherlands.","edition":"5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/B978-0-444-52149-1.00114-2","volume-title":"The yeast, a taxonomic study","author":"Kwon-Chung KJ","year":"2011","unstructured":"Kwon-Chung KJ. 2011. Filobasidiella Kwon-Chung. 1975, p 1443\u20131456. In Kurtzman CP, Fell JW, Boekhout T (ed), The yeast, a taxonomic study, 5th ed. Elsevier Sciences B.V., Amsterdam, Netherlands.","edition":"5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/649858"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.21775\/9781910190012.07","volume-title":"Antifungals: from genomics to resistance and the development of novel agents","author":"Sebolai OM","year":"2015","unstructured":"Sebolai OM, Ogundeji AO. 2015. New antifungal discovery from existing chemical compound collections, p 143\u2013158. In Coste AT, Vandeputte P (ed), Antifungals: from genomics to resistance and the development of novel agents. Caister Academic Press, Norfolk, United Kingdom."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1139\/W07-114"},{"key":"e_1_3_3_9_2","volume-title":"EUCAST definitive document E. Def 7.3: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts","author":"Arendrup MC","year":"2015","unstructured":"Arendrup MC, Guinea J, Cuenca-Estrella M, Meletiadis J, Mouton JW, Lagrou K, Howard SJ, and the Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST). 2015. EUCAST definitive document E. Def 7.3: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts. EUCAST, Copenhagen, Denmark. http:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/AFST\/Files\/EUCAST_E_Def_7_3_Yeast_testing_definitive.pdf."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.01351"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780410001731547"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2307\/3760427"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.12004.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.128322"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.2927"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.05.004"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12544495"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1081\/CLT-100100917"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780330722"},{"key":"e_1_3_3_20_2","first-page":"500","volume-title":"Ibuprofen: discovery, development and therapeutics","author":"Volans G","year":"2015","unstructured":"Volans G. 2015. Human toxicity of ibuprofen, p 500\u2013519. In Rainsford KD (ed), Ibuprofen: discovery, development and therapeutics. Wiley-Blackwell, Oxford, United Kingdom."},{"key":"e_1_3_3_21_2","first-page":"54","article-title":"Ibuprofen overdose","volume":"135","author":"Volans G","year":"2003","unstructured":"Volans G, Monaghan J, Colbridge M. 2003. Ibuprofen overdose. 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