2026-06-14T02:28:55Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/139572024-11-28T12:36:32Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609col_20.500.12105_25179

00925njm 22002777a 4500 dc Lara-Aguilar, Violeta author Rueda Hernandez, Maria Cristina author Garcia-Barbazan, Irene author Varona Fernandez, Sarai author Monzon-Fernandez, Sara author Jimenez Sancho, Maria Pilar author Cuesta de la Plaza, Isabel author Zaballos, Ángel author Zaragoza, Oscar author 2021-12 Candida auris has emerged as a fungal pathogen that causes nosocomial outbreaks worldwide. Diseases caused by this fungus are of concern, due to its reduced susceptibility to several antifungals. C. auris exhibits paradoxical growth (PG; defined as growth at high, but not intermediate antifungal concentrations) in the presence of caspofungin (CPF). We have characterized the cellular changes associated with adaptation to CPF. Using EUCAST AFST protocols, all C. auris isolates tested showed PG to CPF, although in some isolates it was more prominent. Most isolates also showed a trailing effect (TE) to micafungin and anidulafungin. We identified two FKS genes in C. auris that encode the echinocandins target, namely β-1,3-glucan synthase. FKS1 contained the consensus hot-spot (HS) 1 and HS2 sequences. FKS2 only contained the HS1 region which had a change (F635Y), that has been shown to confer resistance to echinocandins in C. glabrata. PG has been characterized in other species, mainly C. albicans, where high CPF concentrations induced an increase in chitin, cell volume and aggregation. In C. auris CPF only induced a slight accumulation of chitin, and none of the other phenomena. RNAseq experiments demonstrated that CPF induced the expression of genes encoding several GPI-anchored cell wall proteins, membrane proteins required for the stability of the cell wall, chitin synthase and mitogen-activated protein kinases (MAPKs) involved in cell integrity, such as BCK2, HOG1 and MKC1 (SLT2). Our work highlights some of the processes induced in C. auris to adapt to echinocandins. Virulence. 2021 Dec;12(1):1400-1417 10.1080/21505594.2021.1927609 2150-5608 Virulence 34180774 http://hdl.handle.net/20.500.12105/13957 Candida auris FKS Chitin Echinocandins Paradoxical growth or Eagle effect Resistance Trailing effect β-1,3-glucans Adaptation of the emerging pathogenic yeast Candida auris to high caspofungin concentrations correlates with cell wall changes