COOPERATION BETWEEN PROTEIN KINASE A (PKA) AND HIGH OSMOLARITY GLYCEROL RESPONSE (HOG) PATHWAYS IS AFFECTING CELL WALL CARBOHYDRATE MOBILIZATION IN ASPERGILLUS FUMIGATUS

Leandro José de Assis; Adriana Manfiolli; Eliciane Mattos; João Henrique Tadini Marilhano Fabri; Iran Malavazi; Laure Nicolas Annick Ries; Gustavo Goldman

Paper Title

Authors

Leandro José de Assis
Adriana Manfiolli
Eliciane Mattos
João Henrique Tadini Marilhano Fabri
Iran Malavazi
Laure Nicolas Annick Ries
Gustavo Goldman

Modality

Abstract

Subject area

Stress in fungal pathogenesis

Publishing Date

15/05/2019

Country of Publishing

Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/isfus/158969-cooperation-between-protein-kinase-a-(pka)-and-high-osmolarity-glycerol-response-(hog)-pathways-is-affecting-cell

ISBN

978-85-5722-210-6

Keywords

MAPK, PKA, SakA, MpkC, PkaR

Summary

Aspergillus fumigatus is an opportunistic human pathogen causing allergic reactions or systemic infections such as invasive pulmonary aspergillosis especially in immunocompromised patients. The fungal cell wall is the main component responsible for recognition by immune system, due to the specific composition of polysaccharide carbohydrates exposed on the surface of the fungal cell wall called pathogen-associated molecular patterns (PAMPs). Key enzymes in the fungal cell wall biosynthesis are a good target for fungal drug development. This report elucidates the cooperation between HOG and PKA pathways and the mobilization of carbohydrates from storage for fungal cell wall biosynthesis. We suggest that the reduced mobilization of simple sugars causes defects in the structure of the fungal cell wall. Aspergillus fumigatus mitogen-activated protein kinases (MAPKs) are involved in maintaining the normal morphology of the cell wall and providing resistance against cell wall-damaging agents. Upon cell wall stress, cell wall-related sugars need to be synthesized from carbohydrate storage compounds. Here we show that this process is dependent of cAMP-dependent protein kinase A (PKA) activity and regulated by high osmolarity glycerol response (HOG) MAPKs SakA and MpkC. These protein kinases are necessary for normal accumulation/degradation of trehalose and glycogen, and the lack of these genes reduces glucose uptake and glycogen synthesis. The reduced glycogen synthesis was observed for SakA and MpkC mutants, which also displayed alterations in carbohydrates exposition on the cell wall. Carbohydrate mobilization is controlled by SakA interaction with PkaC1 and PkaR, suggesting a putative mechanism where the PkaR regulatory subunit leaves the complex and releases the SakA/PkaC1 complex for activation of enzymes involved in carbohydrate mobilization. In summary, we propose that SakA and MpkC are important for the modulation of PKA activity, therefore regulating the availability and mobilization of monosaccharides for fungal cell wall biosynthesis during cell wall damage and osmotic stress response. This work reveals the interconnection between HogA and PKA pathway for carbohydrate mobilization for cell wall construction.

Title of the Event: III International Symposium on Fungal Stress – ISFUS
City of the Event: São José dos Campos
Title of the Proceedings of the event: Annals of the International Symposium on Fungal Stress – ISFUS
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

ASSIS, Leandro José de et al.. COOPERATION BETWEEN PROTEIN KINASE A (PKA) AND HIGH OSMOLARITY GLYCEROL RESPONSE (HOG) PATHWAYS IS AFFECTING CELL WALL CARBOHYDRATE MOBILIZATION IN ASPERGILLUS FUMIGATUS.. In: Annals of the International Symposium on Fungal Stress – ISFUS. Anais...São José dos Campos(SP) Hotel Nacional Inn, 2019. Available in: https//www.even3.com.br/anais/ISFUS/158969-COOPERATION-BETWEEN-PROTEIN-KINASE-A-(PKA)-AND-HIGH-OSMOLARITY-GLYCEROL-RESPONSE-(HOG)-PATHWAYS-IS-AFFECTING-CELL. Access in: 28/06/2025