Deciphering Cargo Contents in Extracellular Vesicles of Candida haemulonii var. vulnera

ABSTRACTCandida haemulonii comprises a group of pathogenic fungi known for their resistance to primary antifungal treatments. Infections caused by these pathogens present substantial challenges due to the difficulties in accurate identification. Extracellular vesicles (EVs) released by these fungi play a critical role in the pathogen-host interaction, potentially influencing antifungal resistance and virulence. Previous research by our group indicates that EVs contain immunogenic particles capable of impacting the hosts immune response. Understanding the composition of these EVs is crucial for elucidating the mechanisms underlying resistance and virulence in C. haemulonii var. vulnera. This study aims to investigate the contents of EVs from C. haemulonii var. vulnera using proteomic and microRNA sequencing tools, providing insights into their role in adaptation, survival, and the progression of infections. Our findings reveal key proteins transported by EVs, including BMH1, TEF1, CDC19, and PDC11. These proteins are involved in various cellular processes, such as the alteration of cell wall structure, biofilm formation, and facilitation of morphological changes, among others. Additionally, we observed that miRNA-like molecules transported within EVs are linked to the electron transport chain and regulation of the citric acid cycle, which are metabolic processes associated with virulence factors and rapid adaptation to diverse hosts or environments. In this context, our findings provide a novel perspective on fungal EVs, highlighting their potential as targets for therapies. Therefore, these vesicles may reflect the expression levels of regulatory molecules crucial for the survival, pathogenicity, and virulence of C. haemulonii var. vulnera. IMPORTANCEThe study of Candida haemulonii complex holds substantial clinical significance due to its notable resistance to conventional antifungal therapies and the complex challenges inherent in its specific identification. This research focuses on cargo of EVs released by these fungi, which play an essential role in pathogen-host interactions, influencing fungal pathogenicity. EVs contain immunogenic particles that can modulate the hosts immune response. Proteomic and microRNA analyses of EVs from Candida haemulonii var. vulnera have identified key proteins and miRNAs involved in cellular processes such as metabolic adjustment, biofilm formation, and modulation of cytoplasmic functions. These components are essential for the adaptation, survival, and progression of infections. This study offers novel insights into fungal EVs, underscoring their potential as targets for therapeutic intervention. By elucidating the mechanisms underlying the rapid adaptation of Candida haemulonii, the research enhances our understanding of the pathogenicity of this emerging yeast.