Traversing the Cell Wall: The Chitinolytic Activity of Histoplasma capsulatum Extracellular Vesicles Facilitates Their Release

• Published in: Journal of fungi (Basel) Vol. 9; no. 11; p. 1052
• Main Authors: Valdez, Alessandro F, de Souza, Taiane Nascimento, Bonilla, Jhon Jhamilton Artunduaga, Zamith-Miranda, Daniel, Piffer, Alicia Corbellini, Araujo, Glauber R S, Guimarães, Allan J, Frases, Susana, Pereira, Alana Kelyene, Fill, Taicia Pacheco, Estevao, Igor L, Torres, Angel, Almeida, Igor C, Nosanchuk, Joshua D, Nimrichter, Leonardo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.10.2023
• Subjects: Caffeine; Cell walls; Chitinase; Enzymes; Extracellular vesicles; Histoplasma capsulatum; Histoplasmosis; Medical prognosis; methylxanthine; Morphology; Proteins; Transmission electron microscopy; Virulence; Yeast; United States > US; caffeine; chitinase; extracellular vesicles; exosomes; Histoplasma capsulatum; methylxanthine; histoplasmosis
• ISSN: 2309-608X; 2309-608X
• DOI: 10.3390/jof9111052

is the causative agent of histoplasmosis. Treating this fungal infection conventionally has significant limitations, prompting the search for alternative therapies. In this context, fungal extracellular vesicles (EVs) hold relevant potential as both therapeutic agents and targets for the treatment of fungal infections. To explore this further, we conducted a study using pharmacological inhibitors of chitinase (methylxanthines) to investigate their potential to reduce EV release and its subsequent impact on fungal virulence in an in vivo invertebrate model. Our findings revealed that a subinhibitory concentration of the methylxanthine, caffeine, effectively reduces EV release, leading to a modulation of virulence. To the best of our knowledge, this is the first reported instance of a pharmacological inhibitor that reduces fungal EV release without any observed fungicidal effects.