Calcineurin-mediated regulation of hyphal growth, septation, and virulence in Aspergillus fumigatus.

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Juvvadi, PR; Lamoth, F; Steinbach, WJ

Published Date

  • December 2014

Published In

Volume / Issue

  • 178 / 5-6

Start / End Page

  • 341 - 348

PubMed ID

  • 25118871

Pubmed Central ID

  • 25118871

Electronic International Standard Serial Number (EISSN)

  • 1573-0832

Digital Object Identifier (DOI)

  • 10.1007/s11046-014-9794-9

Language

  • eng

Conference Location

  • Netherlands