{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:21:59Z","timestamp":1789474919784,"version":"build-2803163510"},"reference-count":42,"publisher":"American Chemical Society (ACS)","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["Candidomics - P-33425"],"award-info":[{"award-number":["Candidomics - P-33425"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["ChromFunVir - P-32582-B08"],"award-info":[{"award-number":["ChromFunVir - P-32582-B08"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["FWF-SFB70-08"],"award-info":[{"award-number":["FWF-SFB70-08"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["TissueHome  FWF-DOC32-B28"],"award-info":[{"award-number":["TissueHome  FWF-DOC32-B28"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001704","name":"European Society of Clinical Microbiology and Infectious Diseases","doi-asserted-by":"publisher","award":["ESCMID Research Grant 2023"],"award-info":[{"award-number":["ESCMID Research Grant 2023"]}],"id":[{"id":"10.13039\/501100001704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016234","name":"ASEAN-European Academic University Network","doi-asserted-by":"publisher","award":["Bernd Rode Award 2024"],"award-info":[{"award-number":["Bernd Rode Award 2024"]}],"id":[{"id":"10.13039\/100016234","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016234","name":"ASEAN-European Academic University Network","doi-asserted-by":"publisher","award":["Ernst Mach Grant"],"award-info":[{"award-number":["Ernst Mach Grant"]}],"id":[{"id":"10.13039\/100016234","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"crossref","award":["R01AI182977"],"award-info":[{"award-number":["R01AI182977"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Candida auris is an emerging fungal pathogen causing invasive infections in immunocompromised patients, with mortality rates reaching up to 60%. Pronounced drug resistance makes treatment failure common, and so does antifungal tolerance, a phenomenon enabling pathogen survival at supra-MIC concentrations without resistance mutations. Here, we uncover a mechanism of antifungal tolerance in C. auris engaging the mitochondrial cytochrome bc1 complex. Deletion of RIP1, a conserved catalytic complex subunit, does not significantly alter the susceptibility to caspofungin or voriconazole. However, rip1\u0394 mutants exhibit a marked reduction in antifungal tolerance across a wide range of supra-MIC concentrations. Transcriptomics reveals the dysregulation of multiple drug resistance and tolerance-related genes in the rip1\u0394 mutant, demonstrating a role for Rip1 in controlling antifungal susceptibility. Targeting cytochrome bc1 function with the fungal-specific inhibitor Inz-5 enhances antifungal action of both voriconazole and caspofungin. Additionally, ablation of RIP1 causes fitness defects, suggesting that cytochrome bc1 is a potential antifungal target against C. auris infections.<\/jats:p>","DOI":"10.1021\/acsinfecdis.5c01058","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:06:38Z","timestamp":1785423998000},"source":"Crossref","is-referenced-by-count":1,"title":["Cytochrome\n                    <i>bc1<\/i>\n                    Catalytic Subunit\nRip1 Modulates Antifungal Tolerance in\n                    <i>Candida auris<\/i>"],"prefix":"10.1021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6399-0959","authenticated-orcid":true,"given":"Trinh","family":"Phan-Canh","sequence":"first","affiliation":[{"name":"Max Perutz Laboratories Vienna, Vienna BioCenter Campus (VBC) , Dr. Bohr-Gasse 9 , ,","place":["Vienna, Austria, 1030"]},{"name":"Medical University of Vienna , , Dr. Bohr-Gasse 9 , ,","place":["Vienna, Austria, 1030"]},{"name":"Medical University of Innsbruck , , Scho\u0308pfstra\u00dfe 41 , ,","place":["Innsbruck, Austria, 6020"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Lackner","sequence":"additional","affiliation":[{"name":"Medical University of Innsbruck , , Scho\u0308pfstra\u00dfe 41 , ,","place":["Innsbruck, Austria, 6020"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manju","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Hackensack Meridian Health , , 111 Ideation Way , , ,","place":["Nutley, New Jersey, United States, 07110"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Maria","family":"Zenz","sequence":"additional","affiliation":[{"name":"Medical University of Innsbruck , , Scho\u0308pfstra\u00dfe 41 , ,","place":["Innsbruck, Austria, 6020"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Hackensack Meridian Health , , 111 Ideation Way , , ,","place":["Nutley, New Jersey, United States, 07110"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kuchler","sequence":"additional","affiliation":[{"name":"Max Perutz Laboratories Vienna, Vienna BioCenter Campus (VBC) , Dr. Bohr-Gasse 9 , ,","place":["Vienna, Austria, 1030"]},{"name":"Medical University of Vienna , , Dr. Bohr-Gasse 9 , ,","place":["Vienna, Austria, 1030"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"issue":"7","key":"2026073011062896900_cit1","doi-asserted-by":"publisher","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global\nIncidence and Mortality of Severe Fungal Disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect. Dis."},{"issue":"4","key":"2026073011062896900_cit2","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical Practice\nGuideline for the Management of Candidiasis: 2016 Update by the Infectious\nDiseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin. Infect. Dis."},{"issue":"2","key":"2026073011062896900_cit3","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03333-20","article-title":"Genome-Wide Analysis\nof Experimentally Evolved Candida auris Reveals Multiple\nNovel Mechanisms of Multidrug Resistance","volume":"12","author":"Carolus","year":"2021","journal-title":"mBio"},{"issue":"20","key":"2026073011062896900_cit4","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1056\/NEJMra2402635","article-title":"Candida auris Infections","volume":"391","author":"Lionakis","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"2026073011062896900_cit5","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00187-22","article-title":"Candida auris: Host\nInteractions, Antifungal Drug Resistance, and Diagnostics","author":"Chowdhary","year":"2025","journal-title":"Microbiol. Mol. Biol. Rev."},{"issue":"6","key":"2026073011062896900_cit6","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41579-019-0322-2","article-title":"Drug Resistance and Tolerance in Fungi","volume":"18","author":"Berman","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"2026073011062896900_cit7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.drup.2015.10.001","article-title":"Defining the Frontiers\nbetween Antifungal Resistance,\nTolerance and the Concept of Persistence","volume":"23","author":"Delarze","year":"2015","journal-title":"Drug\nResist. Updat."},{"issue":"3","key":"2026073011062896900_cit8","doi-asserted-by":"publisher","first-page":"898","DOI":"10.3390\/biomedicines11030898","article-title":"Identification and Elimination of Antifungal Tolerance in Candida auris","volume":"11","author":"Rasouli Koohi","year":"2023","journal-title":"Biomedicines"},{"issue":"1","key":"2026073011062896900_cit9","doi-asserted-by":"publisher","first-page":"5052","DOI":"10.1038\/s41598-019-41513-6","article-title":"Gene Duplication\nAssociated with Increased Fluconazole Tolerance in Candida auris Cells of Advanced Generational Age","volume":"9","author":"Bhattacharya","year":"2019","journal-title":"Sci. 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Agents Chemother."},{"issue":"8","key":"2026073011062896900_cit13","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1128\/AAC.44.8.2081-2085.2000","article-title":"Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal\nSusceptibility Test Results and In Vivo Outcome after Fluconazole\nTreatment in a Murine Model of Invasive Candidiasis","volume":"44","author":"Arthington-Skaggs","year":"2000","journal-title":"Antimicrob. 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Microbiol."},{"issue":"1","key":"2026073011062896900_cit16","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02529-18","article-title":"Genetic Analysis\nof Candida auris Implicates Hsp90 in Morphogenesis\nand Azole Tolerance and Cdr1 in Azole Resistance","volume":"10","author":"Kim","year":"2019","journal-title":"mBio"},{"issue":"5","key":"2026073011062896900_cit17","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1128\/AAC.48.5.1600-1613.2004","article-title":"Functional Genomic\nAnalysis of Fluconazole\nSusceptibility in the Pathogenic Yeast Candida glabrata: Roles of Calcium Signaling and Mitochondria","volume":"48","author":"Kaur","year":"2004","journal-title":"Antimicrob. 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Microbiol"},{"issue":"9","key":"2026073011062896900_cit22","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1128\/AAC.48.9.3407-3411.2004","article-title":"Paradoxical\nEffect of Caspofungin:\nReduced Activity against Candida albicans at High\nDrug Concentrations","volume":"48","author":"Stevens","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"issue":"6","key":"2026073011062896900_cit23","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00238-18","article-title":"Understanding Echinocandin Resistance\nin the Emerging Pathogen Candida auris","volume":"62","author":"Kordalewska","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"issue":"8","key":"2026073011062896900_cit24","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.chembiol.2016.06.016","article-title":"A Fungal-Selective Cytochrome bc1 Inhibitor\nImpairs Virulence and Prevents the Evolution of Drug Resistance","volume":"23","author":"Vincent","year":"2016","journal-title":"Cell Chem. Biol."},{"issue":"1","key":"2026073011062896900_cit25","doi-asserted-by":"publisher","first-page":"4668","DOI":"10.1038\/s41467-025-59898-6","article-title":"Targeting Epigenetic\nRegulators to Overcome Drug Resistance in the Emerging Human Fungal\nPathogen Candida auris","volume":"16","author":"Zhang","year":"2025","journal-title":"Nat.\nCommun."},{"issue":"4","key":"2026073011062896900_cit26","doi-asserted-by":"publisher","first-page":"e0006722","DOI":"10.1128\/aac.00067-22","article-title":"Deciphering\nthe Mrr1\/Mdr1 Pathway in Azole Resistance of Candida auris","volume":"66","author":"Li","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"issue":"0","key":"2026073011062896900_cit27","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02659-24","article-title":"Gene Dosage of PDR16 Modulates Azole Susceptibility in Candida auris","volume":"0","author":"Phan-Canh","year":"2025","journal-title":"Microbiol. Spectr."},{"issue":"12","key":"2026073011062896900_cit28","doi-asserted-by":"publisher","first-page":"3304","DOI":"10.1038\/s41564-024-01854-z","article-title":"Acquired Amphotericin\nB Resistance Leads to Fitness Trade-Offs That Can Be Mitigated by\nCompensatory Evolution in Candida auris","volume":"9","author":"Carolus","year":"2024","journal-title":"Nat. Microbiol."},{"issue":"5","key":"2026073011062896900_cit29","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02729-21","article-title":"Adenylyl Cyclase and Protein\nKinase a Play Redundant and Distinct Roles in Growth, Differentiation,\nAntifungal Drug Resistance, and Pathogenicity of Candida auris","volume":"12","author":"Kim","year":"2021","journal-title":"mBio"},{"issue":"5","key":"2026073011062896900_cit30","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00973-20","article-title":"The Two-Component\nResponse Regulator Ssk1 and the Mitogen-Activated Protein Kinase Hog1\nControl Antifungal Drug Resistance and Cell Wall Architecture of Candida auris","volume":"5","author":"Shivarathri","year":"2020","journal-title":"mSphere"},{"key":"2026073011062896900_cit31","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/mmi.15379","article-title":"Multi-Omics Analysis\nof Experimentally Evolved Candida auris Isolates\nReveals Modulation of Sterols, Sphingolipids, and Oxidative Stress\nin Acquired Amphotericin B Resistance","volume":"124","author":"Chauhan","year":"2025","journal-title":"Mol.\nMicrobiol."},{"issue":"3","key":"2026073011062896900_cit32","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/s41564-026-02270-1","article-title":"Candida auris Vacuolar Calcium Pump Mediates Fluconazole Efflux and\nResistance Evolution","volume":"11","author":"Song","year":"2026","journal-title":"Nat. Microbiol."},{"issue":"7","key":"2026073011062896900_cit33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1013363","article-title":"The Calcineurin Pathway Regulates\nExtreme Thermotolerance, Cell Membrane and Wall Integrity, Antifungal\nResistance, and Virulence in Candida auris","volume":"21","author":"Cha","year":"2025","journal-title":"PLOS Pathog"},{"issue":"1","key":"2026073011062896900_cit34","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/s41467-025-67022-x","article-title":"Accumulation of Trehalose 6-Phosphate\nin Candidozyma auris Results in Decreased Echinocandin\nResistance and Tolerance","volume":"17","author":"Zhu","year":"2026","journal-title":"Nat. Commun."},{"issue":"1","key":"2026073011062896900_cit35","doi-asserted-by":"publisher","first-page":"7197","DOI":"10.1038\/s41467-021-27545-5","article-title":"Forward\nand Reverse Genetic Dissection of Morphogenesis\nIdentifies Filament-Competent Candida auris Strains","volume":"12","author":"Santana","year":"2021","journal-title":"Nat. Commun."},{"issue":"7","key":"2026073011062896900_cit36","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An Efficient\nGeneral\nPurpose Program for Assigning Sequence Reads to Genomic Features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"issue":"12","key":"2026073011062896900_cit37","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated\nEstimation of Fold Change\nand Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"issue":"43","key":"2026073011062896900_cit38","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene Set\nEnrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide\nExpression Profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci.\nU. S. A."},{"issue":"D1","key":"2026073011062896900_cit39","doi-asserted-by":"publisher","first-page":"D592","DOI":"10.1093\/nar\/gkw924","article-title":"The Candida Genome Database (CGD): Incorporation of\nAssembly 22, Systematic Identifiers and Visualization of High Throughput\nSequencing Data","volume":"45","author":"Skrzypek","year":"2017","journal-title":"Nucleic Acids Res."},{"issue":"3","key":"2026073011062896900_cit40","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0:\nA Universal Enrichment Tool for Interpreting Omics Data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"issue":"11","key":"2026073011062896900_cit41","doi-asserted-by":"publisher","first-page":"3654","DOI":"10.1128\/jcm.02073-15","article-title":"Evaluation\nof the \u201cDip Effect\u201d Phenomenon in Antifungal Susceptibility\nTesting of Candida spp. against Echinocandins by\nUse of Gradient Concentration Strips","volume":"53","author":"Siopi","year":"2015","journal-title":"J. Clin.\nMicrobiol."},{"issue":"6","key":"2026073011062896900_cit42","doi-asserted-by":"publisher","first-page":"DL01","DOI":"10.7860\/JCDR\/2024\/68810.19512","article-title":"Phenomenon of Dip Effect in Antifungal Susceptibility Testing of Candida tropicalis by Using MIC Testing Strips against Echinocandins","volume":"18","author":"Lall","year":"2024","journal-title":"J. Clin. Diagn. Res."}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.5c01058","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/doi\/10.1021\/acsinfecdis.5c01058\/66323331\/acsinfecdis.5c01058.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/doi\/10.1021\/acsinfecdis.5c01058\/66323331\/acsinfecdis.5c01058.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:34:51Z","timestamp":1785429291000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/doi\/10.1021\/acsinfecdis.5c01058\/5236318\/Cytochrome-bc1-Catalytic-Subunit-Rip1-Modulates"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":42,"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.5c01058","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}