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

Histoplasma capsulatum 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 H. capsulatum 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.

Fungal Extracellular Vesicles as a Potential Strategy for Vaccine Development.

Extracellular vesicles (EVs) are released by virtually all live cells. In fungal organisms, the EVs traverse the cell wall and reach the extracellular environment, where they can interact with host cells and potentially impact the disease outcome. Compositional analyses have demonstrated that fungal EVs carry lipids, proteins, polysaccharides, glycans, nucleic acids, and a diversity of small metabolites. Among this variety of compounds, several molecules with immunogenic properties were characterized. It corroborates with their ability to stimulate innate immune cells, induce antibody production and protect insects and mice against fungal infections. In this chapter, we discuss the advantages of using fungal EVs as a new platform for the development of antifungal vaccines.

Encapsulation of Silver Nanoparticles in Polylactic Acid or Poly(lactic-co-glycolic acid) and Their Antimicrobial and Cytotoxic Activities.

Encapsulation with biodegradable polymers is an alternative to reduce adverse effects and improve the physicochemical properties of metallic nanoparticles. In this study, spherical polymeric nanoparticles with an average size of 200 nm loaded with silver nanoparticles (AgNPs) were obtained. The antimicrobial activity against Escherichia coli O157:H7, methicillin-resistant Staphylococcus aureus (MRSA), and yeasts as Candida albicans, Candida parapsilosis and Candida guilliermondii was determined. MIC90 values of nanocomposites were between 0.01 to 1 µg/mL, potentialized effect up to 500 times compared to free AgNPs. In addition, cytotoxic effect on 50% of murine fibroblast (CC50) was obtained at a mean concentration of 9.57 µg/mL of AgNPs (up to ~1000 times higher than MIC90). Consequently, the polymeric nanocomposites loaded with AgNPs are a potential alternative in the development of new biocide agents on Candida species and pathogenic bacteria at non-toxic concentrations for mammalian cells such as murine fibroblasts.