Adaptation of the emerging pathogenic yeast Candida auris to high caspofungin concentrations correlates with cell wall changes
| Autor: | Ángel Zaballos, Violeta Lara-Aguilar, Oscar Zaragoza, Sara Monzón, Cristina Rueda, Sarai Varona, Irene García-Barbazán, Pilar Jiménez, Isabel Cuesta |
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| Přispěvatelé: | Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, European Regional Development Fund (ERDF/FEDER) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
trailing effect Antifungal Agents Resistance Immunology Chitin Infectious and parasitic diseases RC109-216 Microbial Sensitivity Tests Microbiology Cell wall echinocandins resistance Echinocandins 03 medical and health sciences chemistry.chemical_compound Caspofungin Cell Wall medicine paradoxical growth or Eagle effect 030304 developmental biology 0303 health sciences FKS biology 030306 microbiology Chitin synthase Candida auris Corpus albicans Paradoxical growth or Eagle effect Trailing effect Infectious Diseases chemistry β-1 3-glucans biology.protein Anidulafungin Parasitology medicine.drug Research Article Research Paper |
| Zdroj: | Virulence article-version (VoR) Version of Record Virulence, Vol 12, Iss 1, Pp 1400-1417 (2021) Repisalud Instituto de Salud Carlos III (ISCIII) |
| ISSN: | 2150-5608 2150-5594 |
| Popis: | 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. This work was funded by grant SAF2017-86192-R from the Ministerio de Ciencia e Innovación, OZ was also sponsored by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/CIII/0004/0003), co-financed by European Development Regional Fund ERDF “A way to achieve Europe”, Operative program Intelligent Growth 2014-2020 and by Red Española de Investigación en Patología Infecciosa (REIPI RD16/CIII/0004/0003). Sí |
| Databáze: | OpenAIRE |
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