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Eukaryotic Cell, April 2009, p. 511-519, Vol. 8, No. 4
1535-9778/09/$08.00+0     doi:10.1128/EC.00336-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Aspergillus fumigatus Calcipressin CbpA Is Involved in Hyphal Growth and Calcium Homeostasis{triangledown} ,{dagger}

Nadthanan Pinchai,1,3 B. Zachary Perfect,1 Praveen Rao Juvvadi,1 Jarrod R. Fortwendel,1,2 Robert A. Cramer Jr.,5 Yohannes G. Asfaw,4 Joseph Heitman,2,6,7 John R. Perfect,2,7 and William J. Steinbach1,2*

Department of Pediatrics, Duke University Medical Center, Durham, North Carolina,1 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina,2 Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,3 Department of Laboratory Animal Resources, Duke University Medical Center, Durham, North Carolina,4 Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana,5 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina,6 Department of Medicine, Duke University Medical Center, Durham, North Carolina7

Received 6 October 2008/ Accepted 11 February 2009

Calcineurin is a conserved protein phosphatase that plays a critical role in Ca2+ signaling and stress responses. Previously, a new class of conserved calcineurin-binding proteins, the calcipressins, was identified. However, the role of these proteins remains controversial, and both inhibitory and stimulatory effects on calcineurin were observed. In this study, we investigate the role of CbpA, the Aspergillus fumigatus member of the calcipressin family, and report that deletion of the cbpA gene resulted in reduced hyphal growth and limited attenuated virulence. Interestingly, under high-calcium-level conditions, the {Delta}cbpA strain displayed improved Ca2+ tolerance compared to the wild-type strain and revealed increased expression of vcxA, chsA, and cnaA, which encode the vacuolar Ca2+/H+ exchanger VcxA, chitin synthase A, and the calcineurin catalytic subunit CnaA, respectively. The increased transcript levels of these three genes were reversed in the presence of the calcineurin inhibitor FK506, indicating a calcineurin-dependent mechanism. Overexpression of cbpA resulted in decreased transcription of vcxA, chsA, and cnaA, associated with wild-type sensitivity to Ca2+. Taken together, our study highlights the importance of CbpA in the regulation of hyphal growth and calcium adaptation of A. fumigatus and provides evidence that CbpA may serve as a feedback inhibitor in some aspects of calcineurin functions.

* Corresponding author. Mailing address: Division of Pediatric Infectious Diseases, Box 3499, Duke University Medical Center, Durham, NC 27710. Phone: (919) 681-1504. Fax: (919) 684-8902. E-mail: stein022{at}mc.duke.edu

{triangledown} Published ahead of print on 27 February 2009.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, April 2009, p. 511-519, Vol. 8, No. 4
1535-9778/09/$08.00+0     doi:10.1128/EC.00336-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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