Fig. 3: Mutated genes of evolved aggregative strains are involved in the regulation of cell division, cytoskeletal properties and cellular polarity.

These genes were independently identified from different evolved aggregative mutant strains. a Number of isolates for each gene mutation. All aggregative mutant strains were recovered from mouse organs initially infected with yeast-form C. auris cells (as shown in Fig. 2). The mutated loci were identified by comparing the genomic sequences of the mutant strains with those of the yeast-form parent strain. b Major biological processes or signaling pathways of the mutated genes (highlighted in red) of the evolved aggregative strains. Cell wall integrity pathway: 14 mutations were identified, including mutations in genes encoding chitin synthase Chs1, GTPase regulator Lrg1, MAPK proteins Dig2, and several cell wall proteins. Cytokinesis: 7 mutations were identified, including mutations in LRG1 and genes encoding the formin protein Bni1, F-BAR protein Hof1, and IQGAP protein. Actin cable and cytoskeleton: 8 mutations were identified, including mutations in genes encoding components of the actin cytoskeleton-regulatory complex Pan1, clathrin and adaptor complex (Apl2, Apl4, Apm1), and the Arp2/3 complex (Arc19). Cellular polarity: 6 mutations were identified, including mutations in LRG1, BNI1, and genes encoding kinases Kin3 and Hsl1 associated with septin formation. RAM pathway: 13 mutations were identified, including mutations in ACE2, CBK1, MOB2, HYM1, KIC1, and CAS4. c Schematic model indicates the cellular functions of the identified mutated genes. Most mutated genes are involved in the regulation of cell budding and/or cell division. The blue strip indicates the septum; red lines indicate actin cables involved in exocytosis; red circles indicate actin patches involved in endocytosis; orange circles indicate septin double rings in endocytosis; the green solid circle indicates protein Bni1; and the peripheral shadow layer indicates the cell wall. Mutated genes identified in this study are highlighted in red. The mutated genes/pathways identified in this study are interconnected and several genes are involved in the regulation of multiple processes. Note that the biological processes or signaling pathways of the C. auris mutated genes shown were predicted based on homology to their S. cerevisiae or C. albicans counterparts (b) and (c).