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The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive <jats:italic>C. auris<\/jats:italic> multicellular aggregative morphology in the murine host during systemic infection. <jats:italic>C. auris<\/jats:italic> aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated <jats:italic>C. auris<\/jats:italic> genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, <jats:italic>C. auris<\/jats:italic> can rapidly evolve a multicellular aggregative morphology via genetic mutations.<\/jats:p>","DOI":"10.1038\/s41467-024-46786-8","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T07:02:45Z","timestamp":1710572565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection"],"prefix":"10.1038","volume":"15","author":[{"given":"Jian","family":"Bing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangyue","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Ennis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-6499","authenticated-orcid":false,"given":"Clarissa J.","family":"Nobile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7961-3488","authenticated-orcid":false,"given":"Changbin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-7295","authenticated-orcid":false,"given":"Haiqing","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4761-7548","authenticated-orcid":false,"given":"Guanghua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,16]]},"reference":[{"key":"46786_CR1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1348-0421.2008.00083.x","volume":"53","author":"K Satoh","year":"2009","unstructured":"Satoh, K., Makimura, K., Hasumi, Y., Nishiyama, Y., Uchida, K. & Yamaguchi, H. 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