{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:43:43Z","timestamp":1793335423339,"version":"4.5.0"},"reference-count":91,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The ability of the fungal pathogen\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    to undergo a yeast-to-hypha transition is believed to be a key virulence factor, as filaments mediate tissue damage. Here, we show that virulence is not necessarily reduced in filament-deficient strains, and the results depend on the infection model used. We generate a filament-deficient strain by deletion or repression of\n                    <jats:italic>EED1<\/jats:italic>\n                    (known to be required for maintenance of hyphal growth). Consistent with previous studies, the strain is attenuated in damaging epithelial cells and macrophages in vitro and in a mouse model of intraperitoneal infection. However, in a mouse model of systemic infection, the strain is as virulent as the wild type when mice are challenged with intermediate infectious doses, and even more virulent when using low infectious doses. Retained virulence is associated with rapid yeast proliferation, likely the result of metabolic adaptation and improved fitness, leading to high organ fungal loads. Analyses of cytokine responses in vitro and in vivo, as well as systemic infections in immunosuppressed mice, suggest that differences in immunopathology contribute to some extent to retained virulence of the filament-deficient mutant. Our findings challenge the long-standing hypothesis that hyphae are essential for pathogenesis of systemic candidiasis by\n                    <jats:italic>C. albicans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-24095-8","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T06:06:11Z","timestamp":1624428371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-0617","authenticated-orcid":false,"given":"Christine","family":"Dunker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Polke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-5793","authenticated-orcid":false,"given":"Bianca","family":"Schulze-Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-6979","authenticated-orcid":false,"given":"Sven","family":"Rudolphi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-1554","authenticated-orcid":false,"given":"A. Elisabeth","family":"Gressler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2742-3156","authenticated-orcid":false,"given":"Tony","family":"Pawlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Prada Salcedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5667-6032","authenticated-orcid":false,"given":"M. Joanna","family":"Niemiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Slesiona-K\u00fcnzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5261-6267","authenticated-orcid":false,"given":"Marc","family":"Swidergall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2212-1511","authenticated-orcid":false,"given":"Ronny","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1886-7625","authenticated-orcid":false,"given":"Thomas","family":"Dandekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-9984","authenticated-orcid":false,"given":"Ilse D.","family":"Jacobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"24095_CR1","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.tim.2013.04.002","volume":"21","author":"GB Huffnagle","year":"2013","unstructured":"Huffnagle, G. B. & Noverr, M. C. The emerging world of the fungal microbiome. Trends Microbiol. 21, 334\u2013341 (2013).","journal-title":"Trends Microbiol."},{"key":"24095_CR2","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s12275-011-1064-7","volume":"49","author":"J Kim","year":"2011","unstructured":"Kim, J. & Sudbery, P. Candida albicans, a major human fungal pathogen. J. Microbiol. 49, 171\u2013177 (2011).","journal-title":"J. Microbiol."},{"key":"24095_CR3","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/cc10290","volume":"15","author":"N Brusselaers","year":"2011","unstructured":"Brusselaers, N., Blot, S. & Vogelaers, D. Deep-seated Candida infections in the intensive care unit. Neth. J. Crit. Care 15, 183\u2013189 (2011).","journal-title":"J. Crit. Care"},{"key":"24095_CR4","unstructured":"Spellberg B., Marr K. A., Filler S. G. Candida: What should clinicians and scientists be talking about? In: Candida and Candidiasis, Second Edition). (American Society of Microbiology, 2012)."},{"key":"24095_CR5","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1086\/599039","volume":"48","author":"DL Horn","year":"2009","unstructured":"Horn, D. L. et al. Epidemiology and outcomes of Candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin. Infect. Dis. 48, 1695\u20131703 (2009).","journal-title":"Clin. Infect. Dis."},{"key":"24095_CR6","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1080\/13693780701218689","volume":"45","author":"J Perlroth","year":"2007","unstructured":"Perlroth, J., Choi, B. & Spellberg, B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol. 45, 321\u2013346 (2007).","journal-title":"Med Mycol."},{"key":"24095_CR7","doi-asserted-by":"publisher","first-page":"e18394","DOI":"10.1371\/journal.pone.0018394","volume":"6","author":"R Martin","year":"2011","unstructured":"Martin, R. et al. The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension. PLoS ONE 6, e18394 (2011).","journal-title":"PLoS ONE"},{"key":"24095_CR8","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1099\/00221287-146-8-1763","volume":"146","author":"JF Ernst","year":"2000","unstructured":"Ernst, J. F. Transcription factors in Candida albicans \u2013 environmental control of morphogenesis. Microbiology 146, 1763\u20131774 (2000).","journal-title":"Microbiology"},{"key":"24095_CR9","doi-asserted-by":"publisher","unstructured":"Cleary I. A. et al. Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis. FEMS Yeast Res. 16, https:\/\/doi.org\/10.1093\/femsyr\/fow011 (2016).","DOI":"10.1093\/femsyr\/fow011"},{"key":"24095_CR10","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1128\/EC.3.5.1076-1087.2004","volume":"3","author":"MC Lorenz","year":"2004","unstructured":"Lorenz, M. C., Bender, J. A. & Fink, G. R. Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot. Cell 3, 1076\u20131087 (2004).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR11","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1046\/j.1462-5822.2002.00179.x","volume":"4","author":"PJ Rooney","year":"2002","unstructured":"Rooney, P. J. & Klein, B. S. Linking fungal morphogenesis with virulence. Cell Microbiol 4, 127\u2013137 (2002).","journal-title":"Cell Microbiol"},{"key":"24095_CR12","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1128\/EC.05085-11","volume":"10","author":"DS Thompson","year":"2011","unstructured":"Thompson, D. S., Carlisle, P. L. & Kadosh, D. Coevolution of morphology and virulence in Candida species. Eukaryot. Cell 10, 1173\u20131182 (2011).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR13","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3389\/fimmu.2017.00629","volume":"8","author":"L Mukaremera","year":"2017","unstructured":"Mukaremera, L., Lee, K. K., Mora-Montes, H. M. & Gow, N. A. R. Candida albicans yeast, pseudohyphal, and hyphal morphogenesis differentially affects immune recognition. Front Immunol. 8, 629\u2013629 (2017).","journal-title":"Front Immunol."},{"key":"24095_CR14","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1128\/EC.2.5.1053-1060.2003","volume":"2","author":"SP Saville","year":"2003","unstructured":"Saville, S. P., Lazzell, A. L., Monteagudo, C. & Lopez-Ribot, J. L. Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot. Cell 2, 1053\u20131060 (2003).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR15","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/S0092-8674(00)80358-X","volume":"90","author":"H-J Lo","year":"1997","unstructured":"Lo, H.-J. et al. Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939\u2013949 (1997).","journal-title":"Cell"},{"key":"24095_CR16","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1038\/sj.emboj.7600195","volume":"23","author":"X Zheng","year":"2004","unstructured":"Zheng, X., Wang, Y. & Wang, Y. Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis. EMBO J. 23, 1845\u20131856 (2004).","journal-title":"EMBO J."},{"key":"24095_CR17","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/genetics\/156.1.31","volume":"156","author":"BR Braun","year":"2000","unstructured":"Braun, B. R., Head, W. S., Wang, M. X. & Johnson, A. D. Identification and characterization of TUP1-regulated genes in Candida albicans. Genetics 156, 31\u201344 (2000).","journal-title":"Genetics"},{"key":"24095_CR18","doi-asserted-by":"publisher","first-page":"4753","DOI":"10.1093\/emboj\/20.17.4753","volume":"20","author":"BR Braun","year":"2001","unstructured":"Braun, B. R., Kadosh, D. & Johnson, A. D. NRG1, a repressor of filamentous growth in C.albicans, is down-regulated during filament induction. EMBO J. 20, 4753\u20134761 (2001).","journal-title":"EMBO J."},{"key":"24095_CR19","doi-asserted-by":"publisher","first-page":"4742","DOI":"10.1093\/emboj\/20.17.4742","volume":"20","author":"AM Murad","year":"2001","unstructured":"Murad, A. M. et al. NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J. 20, 4742\u20134752 (2001).","journal-title":"EMBO J."},{"key":"24095_CR20","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1111\/j.1462-5822.2007.01009.x","volume":"9","author":"K Zakikhany","year":"2007","unstructured":"Zakikhany, K. et al. In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination. Cell Microbiol 9, 2938\u20132954 (2007).","journal-title":"Cell Microbiol"},{"key":"24095_CR21","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1111\/mmi.13526","volume":"103","author":"M Polke","year":"2017","unstructured":"Polke, M. et al. A functional link between hyphal maintenance and quorum sensing in Candida albicans. Mol. Microbiol 103, 595\u2013617 (2017).","journal-title":"Mol. Microbiol"},{"key":"24095_CR22","doi-asserted-by":"publisher","first-page":"e00915","DOI":"10.1128\/mBio.00915-18","volume":"9","author":"S Allert","year":"2018","unstructured":"Allert, S. et al. Candida albicans-induced epithelial damage mediates translocation through intestinal barriers. mBio 9, e00915\u2013e00918 (2018).","journal-title":"mBio"},{"key":"24095_CR23","doi-asserted-by":"publisher","first-page":"3689","DOI":"10.1128\/IAI.70.7.3689-3700.2002","volume":"70","author":"A Felk","year":"2002","unstructured":"Felk, A. et al. Candida albicans hyphal formation and the expression of the Efg1-regulated proteinases Sap4 to Sap6 are required for the invasion of parenchymal organs. Infect. Immun. 70, 3689\u20133700 (2002).","journal-title":"Infect. Immun."},{"key":"24095_CR24","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1086\/323759","volume":"33","author":"M Nucci","year":"2001","unstructured":"Nucci, M. & Anaissie, E. Revisiting the source of candidemia: skin or gut? Clin. Infect. Dis. 33, 1959\u20131967 (2001).","journal-title":"Clin. Infect. Dis."},{"key":"24095_CR25","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jhin.2009.02.009","volume":"72","author":"LN Miranda","year":"2009","unstructured":"Miranda, L. N. et al. Candida colonisation as a source for candidaemia. J. Hosp. Infect. 72, 9\u201316 (2009).","journal-title":"J. Hosp. Infect."},{"key":"24095_CR26","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s00383-011-3023-0","volume":"28","author":"M Owari","year":"2012","unstructured":"Owari, M., Wasa, M., Oue, T., Nose, S. & Fukuzawa, M. Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats. Pediatr. Surg. Int 28, 299\u2013303 (2012).","journal-title":"Pediatr. Surg. Int"},{"key":"24095_CR27","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1371\/journal.ppat.0040035","volume":"4","author":"AY Koh","year":"2008","unstructured":"Koh, A. Y., K\u00f6hler, J. R., Coggshall, K. T., Van Rooijen, N. & Pier, G. B. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathog. 4, e35 (2008).","journal-title":"PLoS Pathog."},{"key":"24095_CR28","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/cmi.12388","volume":"17","author":"S Vautier","year":"2015","unstructured":"Vautier, S. et al. Candida albicans colonization and dissemination from the murine gastrointestinal tract: the influence of morphology and Th17 immunity. Cell Microbiol. 17, 445\u2013450 (2015).","journal-title":"Cell Microbiol."},{"key":"24095_CR29","doi-asserted-by":"publisher","first-page":"857","DOI":"10.2217\/fmb-2018-0012","volume":"13","author":"E Rom\u00e1n","year":"2018","unstructured":"Rom\u00e1n, E., Huertas, B., Prieto, D., D\u00edez-Orejas, R. & Pla, J. TUP1-mediated filamentation in Candida albicans leads to inability to colonize the mouse gut. Future Microbiol. 13, 857\u2013867 (2018).","journal-title":"Future Microbiol."},{"key":"24095_CR30","doi-asserted-by":"publisher","first-page":"3474","DOI":"10.1128\/AAC.45.12.3474-3481.2001","volume":"45","author":"JC Bowman","year":"2001","unstructured":"Bowman, J. C. et al. Quantitative PCR assay to measure Aspergillus fumigatus burden in a murine model of disseminated aspergillosis: demonstration of efficacy of caspofungin acetate. Antimicrob. Agents Chemother. 45, 3474\u20133481 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"24095_CR31","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1111\/j.1462-5822.2004.00439.x","volume":"6","author":"J Naglik","year":"2004","unstructured":"Naglik, J., Albrecht, A., Bader, O. & Hube, B. Candida albicans proteinases and host\/pathogen interactions. Cell Microbiol 6, 915\u2013926 (2004).","journal-title":"Cell Microbiol"},{"key":"24095_CR32","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/abbs\/gmv011","volume":"47","author":"H Du","year":"2015","unstructured":"Du, H., Li, X., Huang, G., Kang, Y. & Zhu, L. The zinc-finger transcription factor, Ofi1, regulates white\u2013opaque switching and filamentation in the yeast Candida albicans. Acta Biochim. Biophys. Sin. 47, 335\u2013341 (2015).","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"24095_CR33","doi-asserted-by":"crossref","unstructured":"Wakade R. S., Ristow L. C., Stamnes M. A., Kumar A., Krysan D. J. The Ndr\/LATS kinase Cbk1 regulates a specific subset of Ace2 functions and suppresses the hypha-to-yeast transition in Candida albicans. mBio 11, e01900\u201320 (2020).","DOI":"10.1128\/mBio.01900-20"},{"key":"24095_CR34","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1128\/EC.00190-09","volume":"8","author":"C Su","year":"2009","unstructured":"Su, C., Li, Y., Lu, Y. & Chen, J. Mss11, a transcriptional activator, is required for hyphal development in Candida albicans. Eukaryot. Cell 8, 1780\u20131791 (2009).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR35","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1128\/EC.00246-08","volume":"8","author":"B Hao","year":"2009","unstructured":"Hao, B. et al. Candida albicans RFX2 encodes a DNA binding protein involved in DNA damage responses, morphogenesis, and virulence. Eukaryot. Cell 8, 627\u2013639 (2009).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR36","doi-asserted-by":"publisher","first-page":"e01269","DOI":"10.1128\/mBio.01269-16","volume":"7","author":"IV Ene","year":"2016","unstructured":"Ene, I. V. et al. Phenotypic profiling reveals that Candida albicans opaque cells represent a metabolically specialized cell state compared to default white cells. mBio 7, e01269\u201301216 (2016).","journal-title":"mBio"},{"key":"24095_CR37","doi-asserted-by":"publisher","first-page":"4468","DOI":"10.1128\/iai.65.11.4468-4475.1997","volume":"65","author":"CA Kvaal","year":"1997","unstructured":"Kvaal, C. A., Srikantha, T. & Soll, D. R. Misexpression of the white-phase-specific gene WH11 in the opaque phase of Candida albicans affects switching and virulence. Infect. Immun. 65, 4468\u20134475 (1997).","journal-title":"Infect. Immun."},{"key":"24095_CR38","doi-asserted-by":"publisher","first-page":"e1001830","DOI":"10.1371\/journal.pbio.1001830","volume":"12","author":"L Tao","year":"2014","unstructured":"Tao, L. et al. Discovery of a \u201cWhite-Gray-Opaque\u201d tristable phenotypic switching system in Candida albicans: roles of non-genetic diversity in host adaptation. PLoS Biol. 12, e1001830 (2014).","journal-title":"PLoS Biol."},{"key":"24095_CR39","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1097\/ALN.0b013e3181cded3f","volume":"112","author":"R McIlroy David","year":"2010","unstructured":"McIlroy David, R., Wagener, G., Lee, H. T. & Riou, B. Biomarkers of acute kidney injury: an evolving domain. Anesthesiology 112, 998\u20131004 (2010).","journal-title":"Anesthesiology"},{"key":"24095_CR40","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/toxsci\/kfs268","volume":"131","author":"VS Sabbisetti","year":"2013","unstructured":"Sabbisetti, V. S. et al. Novel assays for detection of urinary KIM-1 in mouse models of kidney injury. Toxicol. Sci. 131, 13\u201325 (2013).","journal-title":"Toxicol. Sci."},{"key":"24095_CR41","doi-asserted-by":"publisher","first-page":"e0150001","DOI":"10.1371\/journal.pone.0150001","volume":"11","author":"JS Leventhal","year":"2016","unstructured":"Leventhal, J. S. et al. Autophagy limits endotoxemic acute kidney injury and Alters renal tubular epithelial cell cytokine expression. PLoS ONE 11, e0150001 (2016).","journal-title":"PLoS ONE"},{"key":"24095_CR42","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer, M. et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315, 801\u2013810 (2016).","journal-title":"JAMA"},{"key":"24095_CR43","doi-asserted-by":"publisher","first-page":"4265","DOI":"10.1007\/s00018-016-2294-y","volume":"73","author":"D Kadosh","year":"2016","unstructured":"Kadosh, D. Control of Candida albicans morphology and pathogenicity by post-transcriptional mechanisms. Cell Mol. Life Sci. 73, 4265\u20134278 (2016).","journal-title":"Cell Mol. Life Sci."},{"key":"24095_CR44","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/jof4010010","volume":"4","author":"JV Desai","year":"2018","unstructured":"Desai, J. V. Candida albicans hyphae: from growth initiation to invasion. J. Fungi (Basel) 4, 10\u201319 (2018).","journal-title":"J. Fungi (Basel)"},{"key":"24095_CR45","doi-asserted-by":"publisher","first-page":"e1006699","DOI":"10.1371\/journal.ppat.1006699","volume":"13","author":"L B\u00f6hm","year":"2017","unstructured":"B\u00f6hm, L. et al. The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice. PLoS Pathog. 13, e1006699 (2017).","journal-title":"PLoS Pathog."},{"key":"24095_CR46","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.chom.2019.02.008","volume":"25","author":"JN Witchley","year":"2019","unstructured":"Witchley, J. N. et al. Candida albicans morphogenesis programs control the balance between gut commensalism and invasive infection. Cell Host Microbe 25, 432\u2013443.e436 (2019).","journal-title":"Cell Host Microbe"},{"key":"24095_CR47","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1111\/cmi.12495","volume":"18","author":"S Albac","year":"2016","unstructured":"Albac, S. et al. Candida albicans is able to use M cells as a portal of entry across the intestinal barrier in vitro. Cell Microbiol 18, 195\u2013210 (2016).","journal-title":"Cell Microbiol"},{"key":"24095_CR48","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1086\/430952","volume":"192","author":"B Spellberg","year":"2005","unstructured":"Spellberg, B., Ibrahim, A. S., Edwards, J. E. Jr. & Filler, S. G. Mice with disseminated candidiasis die of progressive sepsis. J. Infect. Dis. 192, 336\u2013343 (2005).","journal-title":"J. Infect. Dis."},{"key":"24095_CR49","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1159\/000321157","volume":"3","author":"MS Lionakis","year":"2011","unstructured":"Lionakis, M. S., Lim, J. K., Lee, C. C. & Murphy, P. M. Organ-specific innate immune responses in a mouse model of invasive candidiasis. J. Innate Immun. 3, 180\u2013199 (2011).","journal-title":"J. Innate Immun."},{"key":"24095_CR50","doi-asserted-by":"publisher","first-page":"e17046","DOI":"10.1371\/journal.pone.0017046","volume":"6","author":"B W\u00e4chtler","year":"2011","unstructured":"W\u00e4chtler, B., Wilson, D., Haedicke, K., Dalle, F. & Hube, B. From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells. PLoS ONE 6, e17046 (2011).","journal-title":"PLoS ONE"},{"key":"24095_CR51","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1128\/IAI.00001-10","volume":"78","author":"CG McKenzie","year":"2010","unstructured":"McKenzie, C. G. et al. Contribution of Candida albicans cell wall components to recognition by and escape from murine macrophages. Infect. Immun. 78, 1650\u20131658 (2010).","journal-title":"Infect. Immun."},{"key":"24095_CR52","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1128\/iai.62.4.1199-1206.1994","volume":"62","author":"E Blasi","year":"1994","unstructured":"Blasi, E., Pitzurra, L., Bartoli, A., Puliti, M. & Bistoni, F. Tumor necrosis factor as an autocrine and paracrine signal controlling the macrophage secretory response to Candida albicans. Infect. Immun. 62, 1199\u20131206 (1994).","journal-title":"Infect. Immun."},{"key":"24095_CR53","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.tim.2014.07.001","volume":"22","author":"AJP Brown","year":"2014","unstructured":"Brown, A. J. P., Brown, G. D., Netea, M. G. & Gow, N. A. R. Metabolism impacts upon Candida immunogenicity and pathogenicity at multiple levels. Trends Microbiol 22, 614\u2013622 (2014).","journal-title":"Trends Microbiol"},{"key":"24095_CR54","doi-asserted-by":"publisher","first-page":"e1000612","DOI":"10.1371\/journal.ppat.1000612","volume":"5","author":"C Askew","year":"2009","unstructured":"Askew, C. et al. Transcriptional regulation of carbohydrate metabolism in the human pathogen Candida albicans. PLoS Pathog. 5, e1000612 (2009).","journal-title":"PLoS Pathog."},{"key":"24095_CR55","doi-asserted-by":"publisher","first-page":"e00495","DOI":"10.1128\/mBio.00495-12","volume":"3","author":"D Sandai","year":"2012","unstructured":"Sandai, D. et al. The evolutionary rewiring of ubiquitination targets has reprogrammed the regulation of carbon assimilation in the pathogenic yeast Candida albicans. mBio 3, e00495\u201300412 (2012).","journal-title":"mBio"},{"key":"24095_CR56","doi-asserted-by":"publisher","first-page":"16238","DOI":"10.1038\/nmicrobiol.2016.238","volume":"2","author":"ER Ballou","year":"2016","unstructured":"Ballou, E. R. et al. Lactate signalling regulates fungal \u03b2-glucan masking and immune evasion. Nat. Microbiol 2, 16238\u201316238 (2016).","journal-title":"Nat. Microbiol"},{"key":"24095_CR57","doi-asserted-by":"publisher","first-page":"e1005566","DOI":"10.1371\/journal.ppat.1005566","volume":"12","author":"DS Childers","year":"2016","unstructured":"Childers, D. S. et al. The rewiring of ubiquitination targets in a pathogenic yeast promotes metabolic flexibility, host colonization and virulence. PLoS Pathog. 12, e1005566 (2016).","journal-title":"PLoS Pathog."},{"key":"24095_CR58","doi-asserted-by":"publisher","first-page":"a019695","DOI":"10.1101\/cshperspect.a019695","volume":"4","author":"IV Ene","year":"2014","unstructured":"Ene, I. V., Brunke, S., AJP, Brown & Hube, B. Metabolism in fungal pathogenesis. Cold Spring Harb. Perspect. Med 4, a019695 (2014).","journal-title":"Cold Spring Harb. Perspect. Med"},{"key":"24095_CR59","doi-asserted-by":"publisher","first-page":"e1006144","DOI":"10.1371\/journal.ppat.1006144","volume":"13","author":"P Miram\u00f3n","year":"2017","unstructured":"Miram\u00f3n, P. & Lorenz, M. C. A feast for Candida: metabolic plasticity confers an edge for virulence. PLoS Pathog. 13, e1006144 (2017).","journal-title":"PLoS Pathog."},{"key":"24095_CR60","doi-asserted-by":"publisher","first-page":"e5039","DOI":"10.1371\/journal.pone.0005039","volume":"4","author":"TF Meiller","year":"2009","unstructured":"Meiller, T. F. et al. A novel immune evasion strategy of Candida albicans: proteolytic cleavage of a salivary antimicrobial peptide. PLoS ONE 4, e5039 (2009).","journal-title":"PLoS ONE"},{"key":"24095_CR61","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.molimm.2009.08.019","volume":"47","author":"K Gropp","year":"2009","unstructured":"Gropp, K. et al. The yeast Candida albicans evades human complement attack by secretion of aspartic proteases. Mol. Immunol. 47, 465\u2013475 (2009).","journal-title":"Mol. Immunol."},{"key":"24095_CR62","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1128\/EC.00210-10","volume":"10","author":"L Schild","year":"2011","unstructured":"Schild, L. et al. Proteolytic cleavage of covalently linked cell wall proteins by Candida albicans Sap9 and Sap10. Eukaryot. Cell 10, 98\u2013109 (2011).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR63","first-page":"F223","volume":"244","author":"DP Simpson","year":"1983","unstructured":"Simpson, D. P. Citrate excretion: a window on renal metabolism. Am. J. Physiol. 244, F223\u2013F234 (1983).","journal-title":"Am. J. Physiol."},{"key":"24095_CR64","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.mib.2015.05.007","volume":"27","author":"K Kochanowski","year":"2015","unstructured":"Kochanowski, K., Sauer, U. & Noor, E. Posttranslational regulation of microbial metabolism. Curr. Opin. Microbiol 27, 10\u201317 (2015).","journal-title":"Curr. Opin. Microbiol"},{"key":"24095_CR65","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1128\/EC.05238-11","volume":"11","author":"MD Leach","year":"2012","unstructured":"Leach, M. D. & Brown, A. J. Posttranslational modifications of proteins in the pathobiology of medically relevant fungi. Eukaryot. Cell 11, 98\u2013108 (2012).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR66","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1093\/infdis\/jiz322","volume":"220","author":"M Swidergall","year":"2019","unstructured":"Swidergall, M. et al. Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J. Infect. Dis. 220, 1477\u20131488 (2019).","journal-title":"J. Infect. Dis."},{"key":"24095_CR67","unstructured":"Angeletti S. et al. Plasma neutrophil gelatinase-associated lipocalin (NGAL) in combination with procalcitonin (PCT) and MR-proadrenomedullin (MR-proADM) in the diagnosis and prognosis of sepsis and sepsis associated acute kidney injury. J. Immunol. Tech. Infect. Dis. 5, https:\/\/www.scitechnol.com\/peer-review\/plasma-neutrophil-gelatinaseassociated-lipocalin-ngal-incombination-with-procalcitoninpct-and-mrproadrenomedullinmrproadm-in-the-d-mrMK.php?article_id=4674 (2016)."},{"key":"24095_CR68","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1159\/000348283","volume":"5","author":"SA Horst","year":"2013","unstructured":"Horst, S. A. et al. Prognostic value and therapeutic potential of TREM-1 in Streptococcus pyogenes- induced sepsis. J. Innate Immun. 5, 581\u2013590 (2013).","journal-title":"J. Innate Immun."},{"key":"24095_CR69","doi-asserted-by":"publisher","first-page":"113","DOI":"10.5334\/jbr-btr.1059","volume":"100","author":"Y Boulanger","year":"2016","unstructured":"Boulanger, Y., Ghuysen, M.-S., Nchimi, A., Lewin, M. & Khamis, J. Ultrasound diagnosis and follow-up of neonate renal candidiasis. J. Belg. Soc. Radio. 100, 113\u2013113 (2016).","journal-title":"J. Belg. Soc. Radio."},{"key":"24095_CR70","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1091\/mbc.e07-11-1110","volume":"19","author":"M Banerjee","year":"2008","unstructured":"Banerjee, M. et al. UME6, a novel filament-specific regulator of Candida albicans hyphal extension and virulence. Mol. Biol. Cell 19, 1354\u20131365 (2008).","journal-title":"Mol. Biol. Cell"},{"key":"24095_CR71","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1128\/EC.00291-09","volume":"9","author":"MJ Spiering","year":"2010","unstructured":"Spiering, M. J. et al. Comparative transcript profiling of Candida albicans and Candida dubliniensis identifies SFL2, a C. albicans gene required for virulence in a reconstituted epithelial infection model. Eukaryot. Cell 9, 251\u2013265 (2010).","journal-title":"Eukaryot. Cell"},{"key":"24095_CR72","doi-asserted-by":"publisher","first-page":"e1007316","DOI":"10.1371\/journal.ppat.1007316","volume":"14","author":"AD McCall","year":"2018","unstructured":"McCall, A. D., Kumar, R. & Edgerton, M. Candida albicans Sfl1\/Sfl2 regulatory network drives the formation of pathogenic microcolonies. PLoS Pathog. 14, e1007316 (2018).","journal-title":"PLoS Pathog."},{"key":"24095_CR73","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/ng.605","volume":"42","author":"SM Noble","year":"2010","unstructured":"Noble, S. M., French, S., Kohn, L. A., Chen, V. & Johnson, A. D. Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat. Genet. 42, 590\u2013600 (2010).","journal-title":"Nat. Genet."},{"key":"24095_CR74","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1128\/CVI.00480-08","volume":"16","author":"SP Saville","year":"2009","unstructured":"Saville, S. P., Lazzell, A. L., Chaturvedi, A. K., Monteagudo, C. & Lopez-Ribot, J. L. Efficacy of a genetically engineered Candida albicans tet-NRG1 strain as an experimental live attenuated vaccine against hematogenously disseminated candidiasis. Clin. Vaccin. Immunol. 16, 430\u2013432 (2009).","journal-title":"Clin. Vaccin. Immunol."},{"key":"24095_CR75","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1128\/IAI.00982-07","volume":"76","author":"SP Saville","year":"2008","unstructured":"Saville, S. P., Lazzell, A. L., Chaturvedi, A. K., Monteagudo, C. & Lopez-Ribot, J. L. Use of a genetically engineered strain to evaluate the pathogenic potential of yeast cell and filamentous forms during Candida albicans systemic infection in immunodeficient mice. Infect. Immun. 76, 97\u2013102 (2008).","journal-title":"Infect. Immun."},{"key":"24095_CR76","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1439-0507.2005.01121.x","volume":"48","author":"DM MacCallum","year":"2005","unstructured":"MacCallum, D. M. & Odds, F. C. Temporal events in the intravenous challenge model for experimental Candida albicans infections in female mice. Mycoses 48, 151\u2013161 (2005).","journal-title":"Mycoses"},{"key":"24095_CR77","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1099\/00221287-146-8-1881","volume":"146","author":"FC Odds","year":"2000","unstructured":"Odds, F. C., Van Nuffel, L. & Gow, N. A. R. Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host. Microbiology 146, 1881\u20131889 (2000).","journal-title":"Microbiology"},{"key":"24095_CR78","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2147\/TCRM.S40160","volume":"10","author":"N Yapar","year":"2014","unstructured":"Yapar, N. Epidemiology and risk factors for invasive candidiasis. Ther. Clin. Risk Manag 10, 95\u2013105 (2014).","journal-title":"Ther. Clin. Risk Manag"},{"key":"24095_CR79","doi-asserted-by":"publisher","unstructured":"Ho H.-l. & Haynes K. Candida glabrata: new tools and technologies\u2014expanding the toolkit. FEMS Yeast Res. 15, fov066, https:\/\/doi.org\/10.1093\/femsyr\/fov066 (2015).","DOI":"10.1093\/femsyr\/fov066"},{"key":"24095_CR80","doi-asserted-by":"publisher","first-page":"e00151","DOI":"10.1128\/mSphere.00151-20","volume":"5","author":"G Bravo Ruiz","year":"2020","unstructured":"Bravo Ruiz, G., Ross, Z. K., Gow, N. A. R. & Lorenz, A. Pseudohyphal growth of the emerging pathogen Candida auris Is triggered by genotoxic stress through the S phase checkpoint. mSphere 5, e00151\u201300120 (2020).","journal-title":"mSphere"},{"key":"24095_CR81","doi-asserted-by":"publisher","first-page":"a019794","DOI":"10.1101\/cshperspect.a019794","volume":"5","author":"A Sil","year":"2014","unstructured":"Sil, A. & Andrianopoulos, A. Thermally dimorphic human fungal pathogens-polyphyletic pathogens with a convergent pathogenicity trait. Cold Spring Harb. Perspect. Med 5, a019794 (2014).","journal-title":"Cold Spring Harb. Perspect. Med"},{"key":"24095_CR82","doi-asserted-by":"publisher","first-page":"6712","DOI":"10.1128\/IAI.68.12.6712-6719.2000","volume":"68","author":"H Nakayama","year":"2000","unstructured":"Nakayama, H. et al. Tetracycline-regulatable system to tightly control gene expression in the pathogenic fungus Candida albicans. Infect. Immun. 68, 6712\u20136719 (2000).","journal-title":"Infect. Immun."},{"key":"24095_CR83","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.gene.2004.06.021","volume":"341","author":"O Reu\u00df","year":"2004","unstructured":"Reu\u00df, O., Vik, \u00c5., Kolter, R. & Morschh\u00e4user, J. The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341, 119\u2013127 (2004).","journal-title":"Gene"},{"key":"24095_CR84","first-page":"179","volume":"198","author":"AM Gillum","year":"1984","unstructured":"Gillum, A. M., Tsay, E. Y. H. & Kirsch, D. R. Isolation of the Candida albicans gene for orotidine-5\u2032-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. MGG 198, 179\u2013182 (1984).","journal-title":"MGG"},{"key":"24095_CR85","doi-asserted-by":"publisher","first-page":"W537","DOI":"10.1093\/nar\/gky379","volume":"46","author":"E Afgan","year":"2018","unstructured":"Afgan, E. et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Res. 46, W537\u2013w544 (2018).","journal-title":"Nucleic Acids Res."},{"key":"24095_CR86","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550\u2013571 (2014).","journal-title":"Genome Biol."},{"key":"24095_CR87","doi-asserted-by":"publisher","first-page":"D592","DOI":"10.1093\/nar\/gkw924","volume":"45","author":"MS Skrzypek","year":"2017","unstructured":"Skrzypek, M. S. et al. The Candida Genome Database (CGD): incorporation of Assembly 22, systematic identifiers and visualization of high throughput sequencing data. Nucleic Acids Res. 45, D592\u2013D596 (2017).","journal-title":"Nucleic Acids Res."},{"key":"24095_CR88","doi-asserted-by":"publisher","first-page":"e21800","DOI":"10.1371\/journal.pone.0021800","volume":"6","author":"F Supek","year":"2011","unstructured":"Supek, F., Bo\u0161njak, M., \u0160kunca, N. & \u0160muc, T. REVIGO summarizes and visualizes long lists of gene ontology terms. PLOS ONE 6, e21800 (2011).","journal-title":"PLOS ONE"},{"key":"24095_CR89","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13, 2498\u20132504 (2003).","journal-title":"Genome Res"},{"key":"24095_CR90","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1086\/516455","volume":"175","author":"Y Han","year":"1997","unstructured":"Han, Y. & Cutler, J. E. Assessment of a mouse model of neutropenia and the effect of an anti-candidiasis monoclonal antibody in these animals. J. Infect. Dis. 175, 1169\u20131175 (1997).","journal-title":"J. Infect. Dis."},{"key":"24095_CR91","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1159\/000205281","volume":"1","author":"D Ermert","year":"2009","unstructured":"Ermert, D. et al. Mouse neutrophil extracellular traps in microbial infections. J. Innate Immun. 1, 181\u2013193 (2009).","journal-title":"J. Innate Immun."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-24095-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-24095-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-24095-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T08:05:14Z","timestamp":1669968314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-24095-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,23]]},"references-count":91,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["24095"],"URL":"https:\/\/doi.org\/10.1038\/s41467-021-24095-8","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.740345974.793587335","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,23]]},"assertion":[{"value":"19 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3899"}}