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Calcineurin-mediated regulation of hyphal growth, septation, and virulence in
Aspergillus fumigatus
#MMPMID25118871
Juvvadi PR
; Lamoth F
; Steinbach WJ
Mycopathologia
2014[Dec]; 178
(5-6
): 341-8
PMID25118871
show ga
Calcineurin is a heterodimeric protein phosphatase complex composed of catalytic
(CnaA) and regulatory (CnaB) subunits and plays diverse roles in regulating
fungal stress responses, morphogenesis, and pathogenesis. Fungal pathogens
utilize the calcineurin pathway to survive in the host environment and cause
life-threatening infections. The immunosuppressive calcineurin inhibitors (FK506
and cyclosporine A) are active against fungi, making calcineurin a promising
antifungal drug target. Here, we review novel findings on calcineurin
localization and functions in Aspergillus fumigatus hyphal growth and septum
formation through regulation of proteins involved in cell wall biosynthesis.
Extensive mutational analysis in the functional domains of A. fumigatus CnaA has
led to an understanding of the relevance of these domains for the localization
and function of CnaA at the hyphal septum. An evolutionarily conserved novel mode
of calcineurin regulation by phosphorylation in filamentous fungi was found to be
responsible for virulence in A. fumigatus. This finding of a filamentous
fungal-specific mechanism controlling hyphal growth and virulence represents a
potential target for antifungal therapy.
|*Gene Expression Regulation, Fungal
[MESH]
|Aspergillus fumigatus/*genetics/*growth & development
[MESH]
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