{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:18:55Z","timestamp":1791519535930,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011455","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000}}],"reference-count":102,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI047837"],"award-info":[{"award-number":["R01AI047837"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI177553"],"award-info":[{"award-number":["R01AI177553"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007539"],"award-info":[{"award-number":["T32AI007539"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Human fungal pathogens must survive diverse reactive oxygen species (ROS) produced by host immune cells that can oxidize a range of cellular molecules including proteins, lipids, and DNA. Formation of lipid radicals can be especially damaging, as it leads to a chain reaction of lipid peroxidation that causes widespread damage to the plasma membrane. Most previous studies on antioxidant pathways in fungal pathogens have been conducted with hydrogen peroxide, so the pathways used to combat organic peroxides and lipid peroxidation are not well understood. The most well-known peroxidase in <jats:italic>Candida albicans<\/jats:italic>, catalase, can only act on hydrogen peroxide. We therefore characterized a family of four glutathione peroxidases (GPxs) that were predicted to play an important role in reducing organic peroxides. One of the GPxs, Gpx3 is also known to activate the Cap1 transcription factor that plays the major role in inducing antioxidant genes in response to ROS. Surprisingly, we found that the only measurable role of the GPxs is activation of Cap1 and did not find a significant role for GPxs in the direct detoxification of peroxides. Furthermore, a <jats:italic>CAP1<\/jats:italic> deletion mutant strain was highly sensitive to organic peroxides and oxidized lipids, indicating an important role for antioxidant genes upregulated by Cap1 in protecting cells from organic peroxides. We identified <jats:italic>GLR1<\/jats:italic> (Glutathione reductase), a gene upregulated by Cap1, as important for protecting cells from oxidized lipids, implicating glutathione utilizing enzymes in the protection against lipid peroxidation. Furthermore, an RNA-sequencing study in <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> showed upregulation of a diverse set of antioxidant genes and protein damage pathways in response to organic peroxides. Overall, our results identify novel mechanisms by which <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> responds to oxidative stress resistance which open new avenues for understanding how fungal pathogens resist ROS in the host.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011455","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T17:39:22Z","timestamp":1729532362000},"page":"e1011455","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Candida albicans pathways that protect against organic peroxides and lipid peroxidation"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7296-1316","authenticated-orcid":true,"given":"Kara A.","family":"Swenson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyunghun","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5989-4086","authenticated-orcid":true,"given":"James B.","family":"Konopka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"issue":"Pt 1","key":"pgen.1011455.ref001","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1242\/jeb.088930","article-title":"Stress adaptation in a pathogenic fungus","volume":"217","author":"AJ Brown","year":"2014","journal-title":"J Exp Biol"},{"issue":"1","key":"pgen.1011455.ref002","doi-asserted-by":"crossref","first-page":"e1007911","DOI":"10.1371\/journal.pgen.1007911","article-title":"Plasma membrane architecture protects Candida albicans from killing by copper.","volume":"15","author":"LM Douglas","year":"2019","journal-title":"PLoS Genet"},{"issue":"6","key":"pgen.1011455.ref003","doi-asserted-by":"crossref","first-page":"e0267123","DOI":"10.1128\/mbio.02671-23","article-title":"Candida albicans resistance to hypochlorous acid.","volume":"14","author":"LM Douglas","year":"2023","journal-title":"mBio"},{"issue":"4","key":"pgen.1011455.ref004","article-title":"Stress Adaptation","volume":"5","author":"AJP Brown","year":"2017","journal-title":"Microbiol Spectr"},{"issue":"5","key":"pgen.1011455.ref005","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.tim.2020.09.010","article-title":"Anticipatory Stress Responses and Immune Evasion in Fungal Pathogens","volume":"29","author":"A Pradhan","year":"2021","journal-title":"Trends Microbiol"},{"key":"pgen.1011455.ref006","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3389\/fcimb.2019.00261","article-title":"Stress-Activated Protein Kinases in Human Fungal Pathogens.","volume":"9","author":"AM Day","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"pgen.1011455.ref007","doi-asserted-by":"crossref","first-page":"a019273","DOI":"10.1101\/cshperspect.a019273","article-title":"The spectrum of fungi that infects humans.","volume":"5","author":"JR Kohler","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"pgen.1011455.ref008","article-title":"The pathobiology of human fungal infections","author":"GD Brown","year":"2024","journal-title":"Nat Rev Microbiol"},{"issue":"165","key":"pgen.1011455.ref009","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: human fungal infections.","volume":"4","author":"GD Brown","year":"2012","journal-title":"Sci Transl Med."},{"issue":"5","key":"pgen.1011455.ref010","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41564-022-01112-0","article-title":"Evolution of the human pathogenic lifestyle in fungi","volume":"7","author":"A. 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