, Volume 178, Issue 5–6, pp 341–348 | Cite as

Calcineurin-Mediated Regulation of Hyphal Growth, Septation, and Virulence in Aspergillus fumigatus

  • Praveen R. JuvvadiEmail author
  • Frédéric Lamoth
  • William J. SteinbachEmail author


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.


Calcineurin Aspergillus fumigatus Hyphal growth Septum Virulence 



These studies were funded by NIH/NIAID 1 R56 AI077648-01A2 and 1 R21 AI097541-01A1 Grants to WJS. FL is supported by the Swiss Foundation for Medical-Biological Grants and the Swiss National Science Foundation (P3SMP3-151742).


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Division of Pediatric Infectious Diseases, Department of PediatricsDuke University Medical CenterDurhamUSA
  2. 2.Infectious Diseases Service, Department of MedicineLausanne University HospitalLausanneSwitzerland
  3. 3.Institute of MicrobiologyLausanne University HospitalLausanneSwitzerland
  4. 4.Department of Molecular Genetics and MicrobiologyDuke University Medical CenterDurhamUSA

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