{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:45:10Z","timestamp":1774316710796,"version":"3.50.1"},"reference-count":79,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":319,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 R01AI109025"],"award-info":[{"award-number":["R01 R01AI109025"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Drug-resistant microbes typically carry mutations in genes involved in critical cellular functions and may therefore be less fit under drug-free conditions than susceptible strains. Candida glabrata is a prevalent opportunistic yeast pathogen with a high rate of fluconazole resistance (FLZR), echinocandin resistance (ECR), and multidrug resistance (MDR) relative to other Candida. However, the fitness of C. glabrata MDR isolates, particularly in the host, is poorly characterized, and studies of FLZR isolate fitness have produced contradictory findings. Two important host niches for C. glabrata are macrophages, in which it survives and proliferates, and the gut. Herein, we used a collection of clinical and lab-derived C. glabrata isolates to show that FLZR C. glabrata isolates are less fit inside macrophages than susceptible isolates and that this fitness cost is reversed by acquiring ECR mutations. Interestingly, dual-RNAseq revealed that macrophages infected with drug-resistant isolates mount an inflammatory response whereas intracellular drug-resistant cells downregulate processes required for in-host adaptation. Furthermore, drug-resistant isolates were outcompeted by their susceptible counterparts during gut colonization and in infected kidneys, while showing comparable fitness in the spleen. Collectively, our study shows that macrophage-rich organs, such as the spleen, favor the retention of MDR isolates of C. glabrata.<\/jats:p>","DOI":"10.1093\/femsyr\/foae035","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T10:22:33Z","timestamp":1731666153000},"source":"Crossref","is-referenced-by-count":5,"title":["A multidimensional assessment of in-host fitness costs of drug resistance in the opportunistic fungal pathogen <i>Candida glabrata<\/i>"],"prefix":"10.1093","volume":"24","author":[{"given":"Amir","family":"Arastehfar","sequence":"first","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health , Nutley, NJ 07110 ,","place":["United States"]},{"name":"Division of Infectious Diseases, Massachusetts General Hospital , Boston, MA 02114 ,","place":["United States"]},{"name":"Department of Medicine, Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farnaz","family":"Daneshnia","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health , Nutley, NJ 07110 ,","place":["United States"]},{"name":"Division of Infectious Diseases, Massachusetts General Hospital , Boston, MA 02114 ,","place":["United States"]},{"name":"Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam , Amsterdam1012 WX ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrant","family":"Hovhannisyan","sequence":"additional","affiliation":[{"name":"Life Sciences Programme, Supercomputing Center (BSC-CNS) , 08034 Barcelona ,","place":["Spain"]},{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , 08028 Barcelona ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathaly","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health , Nutley, NJ 07110 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1174-4182","authenticated-orcid":false,"given":"Macit","family":"Ilkit","sequence":"additional","affiliation":[{"name":"Division of Mycology, Department of Microbiology, Faculty of Medicine, University of \u00c7ukurova , 01330 Adana ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jigar V","family":"Desai","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health , Nutley, NJ 07110 ,","place":["United States"]},{"name":"Georgetown University Lombardi Comprehensive Cancer Center , Washington, DC 20057 ,","place":["United 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