Taxonomic group: fungi / Ascomycota
(Phylum: Ascomycota)
Organ / tissue: cell wall,
hyphae
NCBI PubMed ID: 30538182Publication DOI: 10.1128/mBio.01952-18Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: Goldman GH <ggoldman

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Institutions: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil, Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Paulo, Brazil, Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany, Fungal Genetics and Biology Group, School of Life Sciences, University of Nottingham, Nottingham, UK, Geisel School of Medicine at Dartmouth, Department of Microbiology and Immunology, Hanover, New Hampshire, USA, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, Faculty of Life and Environmental Sciences, University of Tsukuba, Japan, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil
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 on cAMP-dependent protein kinase A (PKA) activity and regulated by the 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. Alterations in glycogen synthesis were observed for the sakA and mpkC deletion mutants, which also displayed alterations in carbohydrate exposure 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. This work reveals the communication between the HOG and PKA pathways for carbohydrate mobilization for cell wall construction.IMPORTANCE 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 the 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 the HOG and PKA pathways in the mobilization of carbohydrates for fungal cell wall biosynthesis. We suggest that the reduced mobilization of simple sugars causes defects in the structure of the fungal cell wall. In summary, we propose that SakA is important for PKA activity, therefore regulating the availability and mobilization of monosaccharides for fungal cell wall biosynthesis during cell wall damage and the osmotic stress response.
cell wall, glycogen, Trehalose, Aspergillus fumigatus, MpkC, SakA, high-osmotic glycerol pathway, protein kinase A
Structure type: structural motif or average structure
Location inside paper: p.2, paragraph 2
Trivial name: chitin
Compound class: cell wall polysaccharide, glucan
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_141807,IEDB_151531,IEDB_153212,IEDB_241099,IEDB_423114,IEDB_423150,SB_74,SB_85
Methods: PCR, enzymatic assays
Biological activity: important for correct cell wall structure and organization under osmotic stress
Related record ID(s): 48634, 48636, 48650, 48651, 48653, 48654, 48689, 48691, 48694, 48715, 48752, 48757, 48764, 48769, 48785, 48794, 48795, 48801, 48804, 48828, 48853, 48859, 48872, 48900, 48901, 48902, 48984
NCBI Taxonomy refs (TaxIDs): 746128Reference(s) to other database(s): GTC:G97099AY
Show glycosyltransferases
There is only one chemically distinct structure: