TY - JOUR
T1 - Traversing the Cell Wall
T2 - The Chitinolytic Activity of Histoplasma capsulatum Extracellular Vesicles Facilitates Their Release
AU - Valdez, Alessandro F.
AU - de Souza, Taiane Nascimento
AU - Bonilla, Jhon Jhamilton Artunduaga
AU - Zamith-Miranda, Daniel
AU - Piffer, Alicia Corbellini
AU - Araujo, Glauber R.S.
AU - Guimarães, Allan J.
AU - Frases, Susana
AU - Pereira, Alana Kelyene
AU - Fill, Taicia Pacheco
AU - Estevao, Igor L.
AU - Torres, Angel
AU - Almeida, Igor C.
AU - Nosanchuk, Joshua D.
AU - Nimrichter, Leonardo
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - Histoplasma capsulatum
KW - caffeine
KW - chitinase
KW - exosomes
KW - extracellular vesicles
KW - histoplasmosis
KW - methylxanthine
UR - http://www.scopus.com/inward/record.url?scp=85178111954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85178111954&partnerID=8YFLogxK
U2 - 10.3390/jof9111052
DO - 10.3390/jof9111052
M3 - Article
AN - SCOPUS:85178111954
SN - 2309-608X
VL - 9
JO - Journal of Fungi
JF - Journal of Fungi
IS - 11
M1 - 1052
ER -