Agradecimentos: We thank Carlos Alberto Vieira for technical support. Figure 4 was constructed using Biorender.com (accessed on 8 March 2022). This research was funded by grants from Brazilian agencies São Paulo Research Foundation—FAPESP (proc. no. 2016/03322-7, proc. no. 2021/06794-5, proc. no. 2021/00728-0, proc. no. 2022/02992-0), National Council for Scientific and Technological Development–CNPq (grant no. 420670/2018-1), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Apoio ao Ensino, Pesquisa e Assistência-FAEPA Ver menos

Abstract: Candida albicans is a commensal fungus in healthy humans that causes infection in immunocompromised individuals through the secretion of several virulence factors. The successful establishment of infection is owing to elaborate strategies to cope with defensive molecules secreted by the host, including responses toward oxidative stress. Extracellular vesicle (EV) release is considered an alternative to the biomolecule secretory mechanism that favors fungal interactions with the host cells. During candidiasis establishment, the host environment becomes oxidative, and it impacts EV release and cargo. To simulate the host oxidative environment, we added menadione (an oxidative stress inducer) to the culture medium, and we explored C. albicans EV metabolites by metabolomics analysis. This study characterized lipidic molecules transported to an extracellular milieu by C. albicans after menadione exposure. Through Liquid Chromatography coupled with Mass Spectrometry (LC-MS) analyses, we identified biomolecules transported by EVs and supernatant. The identified molecules are related to several biological processes, such as glycerophospholipid and sphingolipid pathways, which may act at different levels by tuning compound production in accordance with cell requirements that favor a myriad of adaptive responses. Taken together, our results provide new insights into the role of EVs in fungal biology and host-pathogen interactions Ver menos