Candida parapsilosis cell wall proteins—CPAR2_404800 and CPAR2_404780—Are adhesins that bind to human epithelial and endothelial cells and extracellular matrix proteins

Abstract

One of the initial steps necessary for the development of Candida infections is the adherence to the host tissues and cells. Recent transcriptomic studies suggest that, in Candida parapsilosis—a fungal infectious agent that causes systemic candidiasis in immunosuppressed individuals—the adhesion is mediated by pathogen cell‐exposed proteins belonging to the agglutinin‐like sequence (Als) family. However, to date, the actual interactions of individual members of this family with human cells and extracellular matrix (ECM) have not been characterized in detail. In the current study, we focused attention on two of these C. parapsilosis Als proteins—CPAR2_404800 and CPAR2_404780—that were proteomically identified in the fungal cell wall of yeasts grown in the media suitable for culturing human epithelial and endothelial cells. Both proteins were extracted from the cell wall and purified, and using a microplate binding assay and a fluorescence microscopic analysis were shown to adhere to human cells of A431 (epithelial) and HMEC‐1 (endothelial) lines. The human extracellular matrix components that are also plasma proteins—fibronectin and vitronectin—enhanced these interactions, and also could directly bind to CPAR2_404800 and CPAR2_404780 proteins, with a high affinity (KD in a range of 10−7 to 10−8 M) as determined by surface plasmon resonance measurements. Our findings highlight the role of proteins CPAR2_404800 and CPAR2_404780 in adhesion to host cells and proteins, contributing to the knowledge of the mechanisms of host‐pathogen interactions during C. parapsilosis‐caused infections.

Extracellular vesicle production: A bidirectional effect in the interplay between host and Candida fungi

“…In the course of these processes, different molecules produced by the host cells, including proteins or peptides, have a substantial impact on the fungal cells and their virulence mechanisms. The potential influence of various plasma proteins, such as plasminogen, fibronectin, kininogen, vitronectin or complement factors on the adhesive properties of different Candida species has been frequently proposed ( Karkowska-Kuleta et al, 2010 , 2011 , 2016 , 2017 , 2020b ; Kozik et al, 2015 ; Seweryn et al, 2015 ; van der Wielen et al, 2016 ; Zajac et al, 2016 ; Satala et al, 2020 , 2023 ). Furthermore, also the contribution of different host proteins to the formation of biofilms by C. albicans cells has been demonstrated ( Nett et al, 2015 ) .…”