The role of dimorphism regulating histidine kinase (Drk1) in the pathogenic fungus Paracoccidioides brasiliensis cell wall

Translated title
O papel do dimorfismo na regulação da histidina quinase (Drk1) na parede celular do fungo patogênico Paracoccidioides brasiliensis

Publication type
Article
Language
English
Access rights
Open access
Terms of use
CC BY
Appears in Collections:
Metrics
Abstract
Dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM), an endemic disease in Latin America with a high incidence in Brazil. This pathogen presents as infective mycelium at 25 °C in the soil, reverting to its pathogenic form when inhaled by the mammalian host (37 °C). Among these dimorphic fungal species, dimorphism regulating histidine kinase (Drk1) plays an essential role in the morphological transition. These kinases are present in bacteria and fungi but absent in mammalian cells and are important virulence and cellular survival regulators. Hence, the purpose of this study was to investigate the role of PbDrk1 in the cell wall modulation of P. brasiliensis. We observed that PbDrk1 participates in fungal resistance to different cell wall-disturbing agents by reducing viability after treatment with iDrk1. To verify the role of PbDRK1 in cell wall morphogenesis, qPCR results showed that samples previously exposed to iDrk1 presented higher expression levels of several genes related to cell wall modulation. One of them was FKS1, a β-glucan synthase that showed a 3.6-fold increase. Furthermore, confocal microscopy analysis and flow cytometry showed higher β-glucan exposure on the cell surface of P. brasiliensis after incubation with iDrk1. Accordingly, through phagocytosis assays, a significantly higher phagocytic index was observed in yeasts treated with iDrk1 than the control group, demonstrating the role of PbDrk1 in cell wall modulation, which then becomes a relevant target to be investigated. In parallel, the immune response profile showed increased levels of proinflammatory cytokines. Finally, our data strongly suggest that PbDrk1 modulates cell wall component expression, among which we can identify β-glucan. Understanding this signalling pathway may be of great value for identifying targets of antifungal molecular activity since HKs are not present in mammals.
Reference
Navarro MV, Barros YN, Segura WD, Chaves AFA, Jannuzzi GP, Ferreira KS, et al. The role of dimorphism regulating histidine kinase (Drk1) in the pathogenic fungus Paracoccidioides brasiliensis cell wall. Journal of Fungi. 2021 Nov; 7(12):1014. doi:10.3390/jof7121014.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/4085
Journal title
Issue Date
2021


Files in This Item:

jof-07-01014-v2.pdf
Description:
Size: 2.16 MB
Format: Adobe PDF
View/Open
Show full item record

This item is licensed under a Creative Commons License Creative Commons