Deciphering Cargo Contents in Extracellular Vesicles ofCandida haemuloniivar.vulnera
Authors: Oliveira Bianca T. M. , Bitencourt Tamires A. , Santos Patrick W. , Pagano Antônio D. , Pessoni André M. , Rezende Caroline P. , Piraine Renan A. , Masson Ana P. , Faça Vitor , Campos Vinicius F. , Alves Lysangela R. , Colombo Arnaldo L. , Almeida Fausto 
Published: August 2024

ABSTRACTCandida haemuloniicomprises 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 host’s immune response. Understanding the composition of these EVs is crucial for elucidating the mechanisms underlying resistance and virulence inC. haemuloniivar.vulnera. This study aims to investigate the contents of EVs fromC. haemuloniivar.vulnerausing 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 ofC. haemuloniivar.vulnera.IMPORTANCEThe study ofCandida haemuloniicomplex 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 host’s immune response. Proteomic and microRNA analyses of EVs fromCandida haemuloniivar.vulnerahave 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 ofCandida haemulonii, the research enhances our understanding of the pathogenicity of this emerging yeast.