In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 10 ( 2021-10-8), p. e1009817-
Kurzfassung:
The yeast-to-hypha transition is tightly associated with pathogenicity in many human pathogenic fungi, such as the model fungal pathogen Cryptococcus neoformans , which is responsible for approximately 180,000 deaths annually. In this pathogen, the yeast-to-hypha transition can be initiated by distinct stimuli: mating stimulation or glucosamine (GlcN), the monomer of cell wall chitosan. However, it remains poorly understood how the signal specificity for Cryptococcus morphological transition by disparate stimuli is ensured. Here, by integrating temporal expression signature analysis and phenome-based clustering evaluation, we demonstrate that GlcN specifically triggers a unique cellular response, which acts as a critical determinant underlying the activation of GlcN-induced filamentation (GIF). This cellular response is defined by an unusually hyperactive cell wall synthesis that is highly ATP-consuming. A novel cell surface protein Gis1 was identified as the indicator molecule for the GlcN-induced cell wall response. The Mpk1-directed cell wall pathway critically bridges global cell wall gene induction and intracellular ATP supply, ensuring the Gis1-dependent cell wall response and the stimulus specificity of GIF. We further reveal that the ability of Mpk1 to coordinate the cell wall response and GIF activation is conserved in different Cryptococcus pathogens. Phosphoproteomics-based profiling together with genetic and phenotypic analysis revealed that the Mpk1 kinase mediates the regulatory specificity of GIF through a coordinated downstream regulatory network centered on Skn7 and Crz1. Overall, our findings discover an unprecedented and conserved cell wall biosynthesis-dependent fungal differentiation commitment mechanism, which enables the signal specificity of pathogenicity-related dimorphism induced by GlcN in Cryptococcus pathogens.
Materialart:
Online-Ressource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009817
DOI:
10.1371/journal.pgen.1009817.g001
DOI:
10.1371/journal.pgen.1009817.g002
DOI:
10.1371/journal.pgen.1009817.g003
DOI:
10.1371/journal.pgen.1009817.g004
DOI:
10.1371/journal.pgen.1009817.g005
DOI:
10.1371/journal.pgen.1009817.g006
DOI:
10.1371/journal.pgen.1009817.s001
DOI:
10.1371/journal.pgen.1009817.s002
DOI:
10.1371/journal.pgen.1009817.s003
DOI:
10.1371/journal.pgen.1009817.s004
DOI:
10.1371/journal.pgen.1009817.s005
DOI:
10.1371/journal.pgen.1009817.s006
DOI:
10.1371/journal.pgen.1009817.s007
DOI:
10.1371/journal.pgen.1009817.s008
DOI:
10.1371/journal.pgen.1009817.s009
DOI:
10.1371/journal.pgen.1009817.s010
DOI:
10.1371/journal.pgen.1009817.s011
DOI:
10.1371/journal.pgen.1009817.s012
DOI:
10.1371/journal.pgen.1009817.s013
DOI:
10.1371/journal.pgen.1009817.s014
DOI:
10.1371/journal.pgen.1009817.s015
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2021
ZDB Id:
2186725-2
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