{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:57:52Z","timestamp":1791615472608,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lebanese American University Department of Natural Sciences","award":["LX22NP05103"],"award-info":[{"award-number":["LX22NP05103"]}]},{"name":"National Institute of Virology and Bacteriology Program EXCELES","award":["LX22NP05103"],"award-info":[{"award-number":["LX22NP05103"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Background: The pathogenic fungus Candida albicans is a leading agent of death in immunocompromised individuals with a growing trend of antifungal resistance. Methods: The purpose is to induce resistance to drugs in a sensitive C. albicans strain followed by whole-genome sequencing to determine mechanisms of resistance. Strains will be assayed for pathogenicity attributes such as ergosterol and chitin content, growth rate, virulence, and biofilm formation. Results: We observed sequential increases in ergosterol and chitin content in fluconazole-resistant isolates by 78% and 44%. Surface thickening prevents the entry of the drug, resulting in resistance. Resistance imposed a fitness trade-off that led to reduced growth rates, biofilm formation, and virulence in our isolates. Sequencing revealed mutations in genes involved in resistance and pathogenicity such as ERG11, CHS3, GSC2, CDR2, CRZ2, and MSH2. We observed an increase in the number of mutations in key genes with a sequential increase in drug-selective pressures as the organism increased its odds of adapting to inhospitable environments. In ALS4, we observed two mutations in the susceptible strain and five mutations in the resistant strain. Conclusion: This is the first study to induce resistance followed by genotypic and phenotypic analysis of isolates to determine mechanisms of drug resistance.<\/jats:p>","DOI":"10.3390\/jof10050347","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:18:17Z","timestamp":1715599097000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sequential Induction of Drug Resistance and Characterization of an Initial Candida albicans Drug-Sensitive Isolate"],"prefix":"10.3390","volume":"10","author":[{"given":"Setrida","family":"El Hachem","sequence":"first","affiliation":[{"name":"Department of Natural Sciences, Lebanese American University, Byblos P.O. Box 36, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Fattouh","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Lebanese American University, Byblos P.O. Box 36, Lebanon"},{"name":"Department of Biology, Saint George University of Beirut, Beirut 1100-2807, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Chedraoui","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Lebanese American University, Byblos P.O. Box 36, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Finianos","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University Hospital in Pilsen, Charles University, 32300 Pilsen, Czech Republic"},{"name":"Biomedical Center, Faculty of Medicine, Charles University, 32300 Pilsen, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9117-3729","authenticated-orcid":false,"given":"Ibrahim","family":"Bitar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University Hospital in Pilsen, Charles University, 32300 Pilsen, Czech Republic"},{"name":"Biomedical Center, Faculty of Medicine, Charles University, 32300 Pilsen, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5402-7730","authenticated-orcid":false,"given":"Roy A.","family":"Khalaf","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Lebanese American University, Byblos P.O. Box 36, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fattouh, N., Hdayed, D., Geukgeuzian, G., Tokajian, S., and Khalaf, R.A. (2021). Molecular mechanism of fluconazole resistance and pathogenicity attributes of Lebanese Candida albicans hospital isolates. Fungal Genet. Biol., 153.","DOI":"10.1016\/j.fgb.2021.103575"},{"key":"ref_2","unstructured":"Mora Carpio, A.L., and Climaco, A. (2024, February 01). 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