{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:21:45Z","timestamp":1791390105644,"version":"4.3.3"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Ramalingaswami Fellowship","award":["BT\/RLF\/Re-entry\/50\/2019"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/50\/2019"]}]},{"name":"ANRF\/SERB","award":["EEQ\/2022\/000606"],"award-info":[{"award-number":["EEQ\/2022\/000606"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Invasive candidiasis presents a significant healthcare challenge. The human opportunistic fungal pathogen Candida glabrata, a cause of mucosal and deep-seated infections, resists key antifungal drugs and rapidly proliferates within host macrophages, where it withstands high oxidative stress and amino acid starvation. Unlike C. albicans, C. glabrata lacks true hyphae and relies more on stress adaptation mechanisms than filamentation for virulence. This study explores the molecular mechanisms underlying stress adaptations in C. glabrata that contribute to its pathogenicity. Our findings revealed that C. glabrata survives oxidative stress and amino acid starvation more effectively than Saccharomyces cerevisiae, C. albicans, and C. auris. We observed that amino acid starvation and oxidative stress downregulate global protein translation through Gcn2-mediated eukaryotic initiation factor 2\u03b1 phosphorylation, enabling adaptive recovery and activating the transcription factor Gcn4. The gcn2\u0394 and gcn4\u0394 mutants had impaired growth under stress conditions, highlighting the pivotal role of Gcn2\u2013Gcn4 in regulating stress-specific transcripts and promoting fungal survival. Transcriptome sequencing under amino acid starvation conditions demonstrated that Gcn4 orchestrates the expression of a broad array of genes, primarily those involved in stress responses, which are essential for survival during nutrient deprivation. Notably, under oxidative stress, Gcn4 adopts unique adaptation strategies by upregulating a core set of oxidative stress-responsive genes by coordinating a more specialized transcriptional response tailored to oxidative stress. Additionally, gcn2\u0394 and gcn4\u0394 exhibited elevated levels of reactive oxygen species and defective replication within host macrophages, with Gcn4 being crucial in host survival and virulence. This study underscores the importance of translational regulation in stress adaptation of C. glabrata.<\/jats:p>","DOI":"10.1093\/genetics\/iyaf134","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T08:47:51Z","timestamp":1752828471000},"source":"Crossref","is-referenced-by-count":3,"title":["Translation regulation promotes stress adaptation in the human fungal pathogen <i>Candida glabrata<\/i>"],"prefix":"10.1093","volume":"231","author":[{"given":"Aishwarya","family":"Rana","sequence":"first","affiliation":[{"name":"Regional Centre for Biotechnology , 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad 121001 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-2286","authenticated-orcid":false,"given":"Anil","family":"Thakur","sequence":"additional","affiliation":[{"name":"Regional Centre for Biotechnology , 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad 121001 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