Functional redundancy in Candida auris cell surface adhesins crucial for cell-cell interaction and aggregation

Tristan W. Wang, Dimitrios Sofras, Daniel Montelongo-Jauregui, Telmo O. Paiva, Hans Carolus, Yves F. Dufrêne, Areej A. Alfaifi, Carrie McCracken, Vincent M. Bruno, Patrick Van Dijck () and Mary Ann Jabra-Rizk ()
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Tristan W. Wang: University of Maryland
Dimitrios Sofras: KU Leuven
Daniel Montelongo-Jauregui: University of Maryland
Telmo O. Paiva: UCLouvain, Croix du Sud, 4-5, L7.07.07
Hans Carolus: KU Leuven
Yves F. Dufrêne: UCLouvain, Croix du Sud, 4-5, L7.07.07
Areej A. Alfaifi: University of Maryland
Carrie McCracken: University of Maryland School of Medicine
Vincent M. Bruno: School of Medicine University of Maryland
Patrick Van Dijck: KU Leuven
Mary Ann Jabra-Rizk: University of Maryland

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Candida auris is an emerging nosocomial fungal pathogen associated with life-threatening invasive disease due to its persistent colonization, high level of transmissibility and multi-drug resistance. Aggregative and non-aggregative growth phenotypes for C. auris strains with different biofilm forming abilities, drug susceptibilities and virulence characteristics have been described. Using comprehensive transcriptional analysis we identified key cell surface adhesins that were highly upregulated in the aggregative phenotype during in vitro and in vivo grown biofilms using a mouse model of catheter infection. Phenotypic and functional evaluations of generated null mutants demonstrated crucial roles for the adhesins Als4112 and Scf1 in mediating cell-cell adherence, coaggregation and biofilm formation. While individual mutants were largely non-aggregative, in combination cells were able to co-adhere and aggregate, as directly demonstrated by measuring cell adhesion forces using single-cell atomic force spectroscopy. This co-adherence indicates their role as complementary adhesins, which despite their limited similarity, may function redundantly to promote cell-cell interaction and biofilm formation. Functional diversity of cell wall proteins may be a form of regulation that provides the aggregative phenotype of C. auris with flexibility and rapid adaptation to the environment, potentially impacting persistence and virulence.

Date: 2024
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DOI: 10.1038/s41467-024-53588-5

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