Strain and temperature dependent aggregation of Candida auris is attenuated by inhibition of surface amyloid proteins.

Autor: Malavia-Jones D; MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK., Farrer RA; MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK., Stappers MHT; MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK., Edmondson MB; MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK., Borman AM; MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.; UKHSA Mycology Reference Laboratory, National Infection Services, UKHSA South West Laboratory, Science Quarter, Southmead Hospital, Bristol BS10 5NB, UK., Johnson EM; MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.; UKHSA Mycology Reference Laboratory, National Infection Services, UKHSA South West Laboratory, Science Quarter, Southmead Hospital, Bristol BS10 5NB, UK., Lipke PN; Biology Department, Brooklyn College of City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA., Gow NAR; MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.
Jazyk: angličtina
Zdroj: Cell surface (Amsterdam, Netherlands) [Cell Surf] 2023 Jul 24; Vol. 10, pp. 100110. Date of Electronic Publication: 2023 Jul 24 (Print Publication: 2023).
DOI: 10.1016/j.tcsw.2023.100110
Abstrakt: Candida auris is a multi-drug resistant human fungal pathogen that has become a global threat to human health due to its drug resistant phenotype, persistence in the hospital environment and propensity for patient to patient spread. Isolates display variable aggregation that may affect the relative virulence of strains. Therefore, dissection of this phenotype has gained substantial interest in recent years. We studied eight clinical isolates from four different clades (I-IV); four of which had a strongly aggregating phenotype and four of which did not. Genome analysis identified polymorphisms associated with loss of cell surface proteins were enriched in weakly-aggregating strains. Additionally, we identified down-regulation of chitin synthase genes involved in the synthesis of the chitinous septum. Characterisation of the cells revealed no ultrastructural defects in cytokinesis or cell separation in aggregating isolates. Strongly and weakly aggregating strains did not differ in net surface charge or in cell surface hydrophobicity. The capacity for aggregation and for adhesion to polystyrene microspheres were also not correlated. However, aggregation and extracellular matrix formation were all increased at higher growth temperatures, and treatment with the amyloid protein inhibitor Thioflavin-T markedly attenuated aggregation. Genome analysis further indicated strain specific differences in the genome content of GPI-anchored proteins including those encoding genes with the potential to form amyloid proteins. Collectively our data suggests that aggregation is a complex strain and temperature dependent phenomenon that may be linked in part to the ability to form extracellular matrix and cell surface amyloids.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Authors.)
Databáze: MEDLINE
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