title: Aspergillus fumigatus calcipressin CbpA is involved in hyphal growth and calcium homeostasis.
abstract: Calcineurin is a conserved protein phosphatase that plays a critical role in Ca(2+) 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 DeltacbpA strain displayed improved Ca(2+) tolerance compared to the wild-type strain and revealed increased expression of vcxA, chsA, and cnaA, which encode the vacuolar Ca(2+)/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 Ca(2+). 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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Nadthanan
authors.initials: N
authors.lastname: Pinchai
authors.forename: B Zachary
authors.initials: BZ
authors.lastname: Perfect
authors.forename: Praveen Rao
authors.initials: PR
authors.lastname: Juvvadi
authors.forename: Jarrod R
authors.initials: JR
authors.lastname: Fortwendel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cramer
authors.forename: Yohannes G
authors.initials: YG
authors.lastname: Asfaw
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
authors.forename: William J
authors.initials: WJ
authors.lastname: Steinbach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D002118:Calcium / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D025301:Hyphae / Q000737:chemistry / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017384:Sequence Deletion; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D002118:Calcium