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Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses

Nancy A. Chow 1 José F. Muñoz 2 Lalitha Gade 1 Elizabeth L. Berkow 1 Xiao Li 2 Rory M. Welsh 1 Kaitlin Forsberg 1 Shawn R. Lockhart 1 Rodney Adam 3 Alexandre Alanio 4, 5, 6, 7 Ana Alastruey-Izquierdo 8 Sahar Althawadi 9 Ana Belén Araúz 10 Ronen Ben-Ami 11, 12 Amrita Bharat 13 Belinda Calvo 14 Marie Desnos-Ollivier 4, 5 Patricia Escandón 15 Dianne Gardam 16 Revathi Gunturu 3 Christopher H. Heath 16, 17, 18 Oliver Kurzai 19, 20 Ronny Martin 19, 20 Anastasia P. Litvintseva 1, * Christina A. Cuomo 2, * 
Abstract : Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris.
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Submitted on : Monday, May 31, 2021 - 4:33:17 PM
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Nancy A. Chow, José F. Muñoz, Lalitha Gade, Elizabeth L. Berkow, Xiao Li, et al.. Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses. mBio, 2020, 11 (2), pp.e03364-19. ⟨10.1128/mBio.03364-19⟩. ⟨pasteur-03243537⟩



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