Candida auris skin colonization is mediated by Als4112 and interactions with host extracellular matrix proteins
Zhao, G.; Lyu, J.; Veniaminova, N. A.; Zarnowski, R.; Mattos, E.; Johnson, C. J.; Quintanilla, D.; Hautau, H.; Dasgupta, K.; Hold, L. A.; Xu, B.; Anku, J. A. E.; Steltzer, S. S.; Santana, D. J.; Ibrahim, A.; Andes, D.; Nett, J. E.; Singh, S.; Abraham, A. C.; Killian, M. L.; Kahlenberg, J. M.; Wong, S. Y.; O'Meara, T. R.
Show abstract
Candida auris is an often multidrug-resistant fungal pathogen notorious for persistent skin colonization and transmission in healthcare settings. However, the mechanisms driving its adherence to skin remain poorly understood. Here, we developed in vitro systems to allow for detailed analysis of early skin colonization events and identified critical host and pathogen mediators of attachment. Across multiple strains and clades of C. auris, we identified that Als4112, a conserved adhesin, is required for skin colonization via keratinocyte attachment and direct interactions with host extracellular matrix (ECM) proteins, especially basement membrane proteins such as laminin. In a murine epicutaneous infection and human skin explants, deletion of ALS4112 significantly reduced skin colonization, underscoring its essential role in establishing cutaneous persistence. Als4112 also contributes to systemic infection, highlighting the connection between adherence and pathogenicity in this organism. Finally, coating plastic and catheter surfaces with collagen I or III markedly inhibited C. auris attachment and biofilm formation, offering an approach to curb nosocomial transmission. Our study highlights the critical role of Als4112 in C. auris colonization and virulence in vivo, making it an attractive target for future vaccine development. This study also explores the potential of specific collagen coatings as a novel strategy to prevent C. auris adherence to abiotic surfaces, offering new therapeutic avenues to control the spread of C. auris in healthcare settings.
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