Extracellular Vesicles Regulate Biofilm Formation and Yeast-to-Hypha Differentiation in Candida albicans
Leandro Honorato, Joana Feital Demetrio de Araujo, Cameron C. Ellis, Alícia Corbellini Piffer, Yan Pereira, Susana Frasés, Glauber Ribeiro de Sousa Araújo, Bruno Pontes, Maria Tays Mendes, Marcos D. Pereira, Allan J. Guimarães, Natalia Martins da Silva, Gabriele Vargas, Luna S. Joffe, Maurizio Del Poeta, Joshua D. Nosanchuk, Daniel Zamith‐Miranda, Flavia C. G. Reis, Haroldo César de Oliveira, Márcio L. Rodrigues, Sharon de Toledo Martins, Lysangela R. Alves, Igor C. Almeida, Leonardo Nimrichter
Abstract
The ability to undergo morphological changes during adaptation to distinct environments is exploited by Candida albicans and has a direct impact on biofilm formation and virulence. Morphogenesis is controlled by a diversity of stimuli, including osmotic stress, pH, starvation, presence of serum, and microbial components, among others. Apart from external inducers, C. albicans also produces autoregulatory substances. Farnesol and tyrosol are examples of quorum-sensing molecules (QSM) released by C. albicans to regulate yeast-to-hypha conversion. Here, we demonstrate that fungal EVs are messengers impacting biofilm formation, morphogenesis, and virulence in C. albicans. The major players exported in C. albicans EVs included sesquiterpenes, diterpenes, and fatty acids. The understanding of how C. albicans cells communicate to regulate physiology and pathogenesis can lead to novel therapeutic tools to combat candidiasis.