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Cited by 121Fungal and yeast genetics researchAntifungal resistance and susceptibilitySignaling Pathways in Disease

Functional characterization of the Aspergillus fumigatus calcineurin

Ferreira, Márcia Eliana da Silva, Heinekamp, Thorsten, Härtl, Albert, Brakhage, Axel A., Semighini, Camile P., Harris, Steven D., Savoldi, Marcela, de Gouvêa, Paula Fagundes +2 more·2007·Fungal Genetics and Biology
DOI 10.1016/j.fgb.2006.08.004
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Abstract

Aspergillus fumigatus is an aggressive opportunistic pathogen of humans as well as a major allergen. Environmental sensing and retrieving essential nutrients from the environment are general metabolic traits associated with the growth of this saprophytic fungus. Two important mediators of calcium signals in eukaryotic cells are the Ca(2+)-binding protein calmodulin and the Ca(2+)/calmodulin-dependent phosphatase calcineurin. Calcineurin is a heterodimer that consists of a catalytic subunit A and a Ca(2+)/calmodulin binding unit. We deleted the A. fumigatus calA gene, which encodes the calcineurin A catalytic subunit, and demonstrated that this gene is not essential in this fungus. The DeltacalA mutant strain has severe defects in growth extension, branching and conidial architecture. Furthermore, the A. fumigatus DeltacalA mutant strain has decreased fitness in a low dose murine infection and cannot grow in fetal bovine serum (FBS). After potassium phosphate was added to liquid FBS, the DeltacalA mutant strain could grow with the characteristic phenotype of the DeltacalA mutation. When A. fumigatus calcineurin is inhibited by tacrolimus in a phosphate depleted medium, there is a reduction in the inorganic phosphate transport and six putative phosphate transporter genes have altered mRNA levels. However, there is no effect on the acid phosphatase activity. These results suggest that calcineurin is involved in the regulation of the PHO pathway in A. fumigatus. Our work on calcineurin opens new venues for the research on sensing and nutrient acquisition in A. fumigatus.

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  • The C. glabrata Δcnb1 strain phenotype (increased susceptibility to azoles and cell wall-damaging agents, decreased virulence) is consistent with previous findings for other pathogenic fungi.

    “For example, the observed C. glabrata Δcnb1 strain phenotype, which is characterized by an increased susceptibility to azoles and cell wall-damaging agents as well as decreased virulence, is consistent with previous findings for other pathogenic fungi, such as C. albicans (2-4, 27), C. neoformans (11, 18, 21), and A. fumigatus (9, 30).”

    From Roles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of <i>Candida glabrata</i> (2010) · cites this paper as [9]

  • Calcineurin is not an essential gene in A. fumigatus, but it is a key phosphatase involved in regulating differentiation and fitness of this opportunistic pathogen.

    “Though calcineurin is not an essential gene in A. fumigatus, it is a key phosphatase involved in regulating the differentiation and fitness of this opportunistic pathogen (Ferreira et al., 2007; Steinbach et al., 2006).”

    From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Ferreira et al., 2007

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Authors
Ferreira, M. E. D. S., Heinekamp, T., Härtl, A., Brakhage, A. A., Semighini, C. P., Harris, S. D., Savoldi, M., de Gouvêa, P. F., Goldman, M. H. D. S., & Goldman, G. H.
Affiliations
  • Universidade de São Paulo (BR)
  • Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
  • University of Nebraska–Lincoln (US)
Corresponding author
Goldman, Gustavo H.
ORCID
Venue
Fungal Genetics and Biology
Publisher
Elsevier BV
Published
2007-03
Volume
44
Issue
3
Pages
219-230
ISSN
1087-1845 (ISSN-L)
DOI
10.1016/j.fgb.2006.08.004
OpenAlex
W1988682446
Cited by
121
References
46
Citations by year
2026: 2 · 2025: 1 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 8 · 2016: 12 · 2015: 5 · 2014: 21 · 2013: 7 · 2012: 5
FWCI
3.39
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Fungal Genetics and Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Lincoln (University of Nebraska) (submittedVersion)
Funders
Fundação de Amparo à Pesquisa do Estado de São Paulo
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
Aspergillus fumigatus, calcineurin, calcium signaling, phosphate transport, phosphate transporters, nutrient acquisition, acid phosphatase
MeSH terms
Acid Phosphatase, Animals, Aspergillus fumigatus, Cattle, Culture Media, Fetal Blood, Fungal Proteins, Mice, Inbred BALB C, Microscopy, Electron, Scanning, Mutation, Phosphates, RNA, Messenger, Spores, Fungal, Time Factors, Gene Expression Regulation, Fungal, Tacrolimus, Calcineurin, Reverse Transcriptase Polymerase Chain Reaction, Catalytic Domain, Hyphae, Membrane Transport Proteins, Mice

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