Calvo, B. et al. First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia. J. Infect. 73, 369–374 (2016).
Lockhart, S. R. et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin. Infect. Dis. 64, 134–140 (2017).
Satoh, K. et al. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol. Immunol. 53, 41–44 (2009).
Magobo, R. E., Corcoran, C., Seetharam, S. & Govender, N. P. Candida auris-associated candidemia, South Africa. Emerg. Infect. Dis. 20, 1250 (2014).
Chowdhary, A. et al. Multidrug-resistant endemic clonal strain of Candida auris in India. Eur. J. Clin. Microbiol. Infect. Dis. 33, 919–926 (2014).
Ben-Ami, R. et al. Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel. Emerg. Infect. Dis. 23, 195 (2017).
Gaitán, A. C. R. et al. Nosocomial fungemia by Candida auris: first four reported cases in continental Europe. Rev. Iberoam. Micol. 34, 23–27 (2017).
Schelenz, S. et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob. Resist. Infect. Control 5, 35 (2016).
Morales-López, S. E. et al. Invasive infections with multidrug-resistant yeast Candida auris, Colombia. Emerg. Infect. Dis. 23, 162 (2017).
Li, C. et al. Genetic mutations across multiple pathways drive filamentous growth and virulence in the emerging fungal pathogen Candida auris. Sci. China Life Sci. 68, 2484–2486 (2025).
Alanio, A. et al. First patient-to-patient intrahospital transmission of clade I Candida auris in France revealed after a two-month incubation period. Microbiol. Spectr. 10, e0183322 (2022).
Huang, X. et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29, 210–221.e6 (2021).
Antifungal Susceptibility Testing for C. auris (Centers for Disease Control and Prevention (CDC), 2024).
Ostrowsky, B. Candida auris isolates resistant to three classes of antifungal medications – New York, 2019. MMWR Morb. Mortal. Wkly Rep. 69, 6–9 (2020).
Lyman, M. Notes from the field: transmission of pan-resistant and echinocandin-resistant Candida auris in health care facilities ― Texas and the District of Columbia, January–April 2021. MMWR Morb. Mortal. Wkly Rep. 70, 1022–1023 (2021).
Antibiotic Resistance Threats in the United States (Centers for Disease Control and Prevention (CDC), 2019).
WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action (World Health Organization, 2022).
Vanden Bossche, H., Koymans, L. & Moereels, H. P450 inhibitors of use in medical treatment: focus on mechanisms of action. Pharmacol. Ther. 67, 79–100 (1995).
Perlin, D. S., Rautemaa-Richardson, R. & Alastruey-Izquierdo, A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect. Dis. 17, e383–e392 (2017).
Muñoz, J. F. et al. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat. Commun. 9, 5346 (2018).
Kwon, Y. J. et al. Candida auris clinical isolates from South Korea: identification, antifungal susceptibility, and genotyping. J. Clin. Microbiol. 57, 01624-18 (2019).
Chow, N. A. et al. Tracing the evolutionary history and global expansion of Candida auris using population genomic analyses. mBio 11, 03364-19 (2020).
Rybak, J. M. et al. Mutations in TAC1B: a novel genetic determinant of clinical fluconazole resistance in Candida auris. mBio 11, 00365-20 (2020).
Li, J. et al. Novel ERG11 and TAC1b mutations associated with azole resistance in Candida auris. Antimicrob. Agents Chemother. 65, 02663-20 (2021).
Li, J., Coste, A. T., Bachmann, D., Sanglard, D. & Lamoth, F. Deciphering the Mrr1/Mdr1 pathway in azole resistance of Candida auris. Antimicrob. Agents Chemother. 66, e0006722 (2022).
Chow, E. W. et al. The transcription factor Rpn4 activates its own transcription and induces efflux pump expression to confer fluconazole resistance in Candida auris. mBio 14, e02688-23 (2023).
Gao, J. et al. LncRNA DINOR is a virulence factor and global regulator of stress responses in Candida auris. Nat. Microbiol. 6, 842–851 (2021).
Li, Z. et al. Genome-wide piggyBac transposon-based mutagenesis and quantitative insertion-site analysis in haploid Candida species. Nat. Protoc. 5, 2705–2727 (2020).
Gao, J. et al. Candida albicans gains azole resistance by altering sphingolipid composition. Nat. Commun. 9, 4495 (2018).
Sun, N., Parrish, R. S., Calderone, R. A. & Fonzi, W. A. Unique, diverged, and conserved mitochondrial functions influencing Candida albicans respiration. mBio 10, 00300-19 (2019).
Sun, N. et al. Azole susceptibility and transcriptome profiling in Candida albicans mitochondrial electron transport chain complex I mutants. Antimicrob. Agents Chemother. 57, 532–542 (2013).
Gulshan, K., Schmidt, J. A., Shahi, P. & Moye-Rowley, W. S. Evidence for the bifunctional nature of mitochondrial phosphatidylserine decarboxylase: role in Pdr3-dependent retrograde regulation of PDR5 expression. Mol. Cell. Biol. 28, 5851–5864 (2008).
Hallstrom, T. C. & Moye-Rowley, W. S. Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae. J. Biol. Chem. 275, 37347–37356 (2000).
Traven, A., Wong, J. M., Xu, D., Sopta, M. & Ingles, C. J. Interorganellar communication: altered nuclear gene expression profiles in a yeast mitochondrial DNA mutant. J. Biol. Chem. 276, 4020–4027 (2001).
Tsai, H.-F., Krol, A. A., Sarti, K. E. & Bennett, J. E. Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants. Antimicrob. Agents Chemother. 50, 1384–1392 (2006).
Zhang, X. & Moye-Rowley, W. S. Saccharomyces cerevisiae multidrug resistance gene expression inversely correlates with the status of the Fo component of the mitochondrial ATPase. J. Biol. Chem. 276, 47844–47852 (2001).
Moye-Rowley, W. Retrograde regulation of multidrug resistance in Saccharomyces cerevisiae. Gene 354, 15–21 (2005).
Shingu-Vazquez, M. & Traven, A. Mitochondria and fungal pathogenesis: drug tolerance, virulence, and potential for antifungal therapy. Eukaryot. Cell 10, 1376–1383 (2011).
Brun, S. et al. Mechanisms of azole resistance in petite mutants of Candida glabrata. Antimicrob. Agents Chemother. 48, 1788–1796 (2004).
Hossain, S. et al. Mitochondrial perturbation reduces susceptibility to xenobiotics through altered efflux in Candida albicans. Genetics 219, iyab095 (2021).
Cheng, S., Clancy, C. J., Nguyen, K. T., Clapp, W. & Nguyen, M. H. A Candida albicans petite mutant strain with uncoupled oxidative phosphorylation overexpresses MDR1 and has diminished susceptibility to fluconazole and voriconazole. Antimicrob. Agents Chemother. 51, 1855–1858 (2007).
Thomas, E. et al. Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative stress pathway, iron homeostasis, and ergosterol levels in Candida albicans. Antimicrob. Agents Chemother. 57, 5580–5599 (2013).
Li, J., Brandalise, D., Coste, A. T., Sanglard, D. & Lamoth, F. Exploration of novel mechanisms of azole resistance in Candida auris. Antimicrob. Agents Chemother. 68, e0126524 (2024).
Maesaki, S., Marichal, P., Bossche, H. V., Sanglard, D. & Kohno, S. Rhodamine 6G efflux for the detection of CDR1-overexpressing azole-resistant Candida albicans strains. J. Antimicrob. Chemother. 44, 27–31 (1999).
Cunningham, K. W. & Fink, G. R. Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases. J. Cell Biol. 124, 351–363 (1994).
Sanglard, D., Ischer, F., Marchetti, O., Entenza, J. & Bille, J. Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. Mol. Microbiol. 48, 959–976 (2003).
Juvvadi, P. R. et al. Calcium-mediated induction of paradoxical growth following caspofungin treatment is associated with calcineurin activation and phosphorylation in Aspergillus fumigatus. Antimicrob. Agents Chemother. 59, 4946–4955 (2015).
Liu, F.-f. et al. Calcium signaling mediates antifungal activity of triazole drugs in the Aspergilli. Fungal Genet. Biol. 81, 182–190 (2015).
Li, Y. et al. Mitochondrial dysfunctions trigger the calcium signaling-dependent fungal multidrug resistance. Proc. Natl Acad. Sci. USA 117, 1711–1721 (2020).
Singh, S. D. et al. Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog. 5, e1000532 (2009).
Cunningham, K. W. & Fink, G. R. Calcineurin inhibits VCX 1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae. Mol. Cell. Biol. 16, 2226–2237 (1996).
Rosenberg, A. et al. Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia. Nat. Commun. 9, 2470 (2018).
Berman, J. & Krysan, D. J. Drug resistance and tolerance in fungi. Nat. Rev. Microbiol. 18, 319–331 (2020).
Almagro Armenteros, J. J., Sønderby, C. K., Sønderby, S. K., Nielsen, H. & Winther, O. DeepLoc: prediction of protein subcellular localization using deep learning. Bioinformatics 33, 3387–3395 (2017).
Allen, G. & Green, N. M. A 31-residue tryptic peptide from the active site of the [Ca++]-transporting adenosine triphosphatase of rabbit sarcoplasmic reticulum. FEBS Lett. 63, 188–192 (1976).
Maruyama, K. & MacLennan, D. H. Mutation of aspartic acid-351, lysine-352, and lysine-515 alters the Ca2+ transport activity of the Ca2+-ATPase expressed in COS-1 cells. Proc. Natl Acad. Sci. USA 85, 3314–3318 (1988).
Kühlbrandt, W. Biology, structure and mechanism of P-type ATPases. Nat. Rev. Mol. Cell Biol. 5, 282–295 (2004).
Lutgring, J. D. et al. FDA-CDC Antimicrobial Resistance Isolate Bank: a publicly available resource to support research, development, and regulatory requirements. J. Clin. Microbiol. 56, 01415-17 (2018).
Wang, X. et al. The first isolate of Candida auris in China: clinical and biological aspects. Emerg. Microbes Infect. 7, 93 (2018).
Fan, S. et al. A biological and genomic comparison of a drug-resistant and a drug-susceptible strain of Candida auris isolated from Beijing, China. Virulence 12, 1388–1399 (2021).
Bing, J. et al. A case of Candida auris candidemia in Xiamen, China, and a comparative analysis of clinical isolates in China. Mycology 13, 68–75 (2022).
Simm, C. et al. Disruption of iron homeostasis and mitochondrial metabolism are promising targets to inhibit Candida auris. Microbiol. Spectr. 10, e0010022 (2022).
Paulusma, C. C. et al. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity. Hepatology 47, 268–278 (2008).
Davis, J. A. et al. The lipid flippases ALA4 and ALA5 play critical roles in cell expansion and plant growth. Plant Physiol. 182, 2111–2125 (2020).
Hiraizumi, M., Yamashita, K., Nishizawa, T. & Nureki, O. Cryo-EM structures capture the transport cycle of the P4-ATPase flippase. Science 365, 1149–1155 (2019).
Andersen, J. P. et al. P4-ATPases as phospholipid flippases—structure, function, and enigmas. Front. Physiol. 7, 275 (2016).
Axelsen, K. B. & Palmgren, M. G. Evolution of substrate specificities in the P-type ATPase superfamily. J. Mol. Evol. 46, 84–101 (1998).
Sonntag, Y. et al. Mutual adaptation of a membrane protein and its lipid bilayer during conformational changes. Nat. Commun. 2, 304 (2011).
Hemenway, C. S. & Heitman, J. Calcineurin: structure, function, and inhibition. Cell Biochem. Biophys. 30, 115–151 (1999).
Rusnak, F. & Mertz, P. Calcineurin: form and function. Physiol. Rev. 80, 1483–1521 (2000).
Cowen, L. E., Carpenter, A. E., Matangkasombut, O., Fink, G. R. & Lindquist, S. Genetic architecture of Hsp90-dependent drug resistance. Eukaryot. Cell 5, 2184–2188 (2006).
Cowen, L. E. & Lindquist, S. Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309, 2185–2189 (2005).
Goldman, A. et al. The calcineurin signaling network evolves via conserved kinase-phosphatase modules that transcend substrate identity. Mol. Cell 55, 422–435 (2014).
Park, H.-S. et al. Calcineurin targets involved in stress survival and fungal virulence. PLoS Pathog. 12, e1005873 (2016).
Lew-Smith, J., Binkley, J. & Sherlock, G. The Candida Genome Database: annotation and visualization updates. Genetics 229, iyaf001 (2025).
Engel, S. R. et al. Saccharomyces Genome Database: advances in genome annotation, expanded biochemical pathways, and other key enhancements. Genetics 229, iyae185 (2025).
Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the \({2}^{-\varDelta \varDelta {C}_{{\rm{T}}}}\) method. Methods 25, 402–408 (2001).
Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907–915 (2019).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Xie, J. L., Singh-Babak, S. D. & Cowen, L. E. Minimum inhibitory concentration (MIC) assay for antifungal drugs. Bio Protoc. 2, e252 (2012).
Agyare-Tabbi, M. R. et al. The putative error prone polymerase REV1 mediates DNA damage and drug resistance in Candida albicans. npj Antimicrob. Resist. 2, 42 (2024).
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).
Kozlov, A. M., Darriba, D., Flouri, T., Morel, B. & Stamatakis, A. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 35, 4453–4455 (2019).
Geiser, J. R., van Tuinen, D., Brockerhoff, S. E., Neff, M. M. & Davis, T. N. Can calmodulin function without binding calcium? Cell 65, 949–959 (1991).