Calcineurin Inhibition or Mutation Enhances Cell Wall Inhibitors against Aspergillus fumigatus

Steinbach, William J.; Cramer, Robert A.; Perfect, B. Zachary; Henn, Christina; Nielsen, Kirsten; Heitman, Joseph; Perfect, John R.

doi:10.1128/aac.01394-06

Cited by 108Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Calcineurin Inhibition or Mutation Enhances Cell Wall Inhibitors against Aspergillus fumigatus

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Steinbach, William J., Cramer, Robert A., Perfect, B. Zachary, Henn, Christina, Nielsen, Kirsten, Heitman, Joseph, Perfect, John R.·2007·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.01394-06PMC PMC1932494

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Abstract

Calcineurin mutation or inhibition enhanced the antifungal morphological effect of cell wall inhibitors caspofungin or nikkomycin Z against Aspergillus fumigatus . Quantification of 1,3-β- d -glucan revealed decreased amounts in the calcineurin A (Δ cnaA ) mutant. Calcineurin can be an excellent adjunct therapeutic target in combination with other cell wall inhibitors against A. fumigatus .

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Calcineurin also increases echinocandin tolerance in C. albicans and A. fumigatus.
“As calcineurin also increases echinocandin tolerance in C. albicans and A. fumigatus (45, 46)”
From Echinocandin tolerance and persistence in vitro are regulated by calcineurin signaling in Candida glabrata (2026) · cites this paper as [45]
The Abstract reports that inhibiting or mutating calcineurin enhanced caspofungin’s antifungal effect against A. fumigatus, supporting the A. fumigatus part of the claim. Our copy does not establish that calcineurin increases echinocandin tolerance in C. albicans. (LLM, conf=0.87)
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[9]Perfect, J. R., K. A. Wright, and R. F. Hector. 1992. Synergistic interaction of nikkomycin and cilofungin against diverse fungi, p. 369-379. In H. Yamaguchi, G. S. Kobayashi, and H. Takahashi (ed.), Recent progress in antifungal chemotherapy. Marcel-Dekker, Inc., New York, NY.

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Authors: Steinbach, W. J., Cramer, R. A., Perfect, B. Z., Henn, C., Nielsen, K., Heitman, J., & Perfect, J. R.
Affiliations: Division of Pediatric Infectious Diseases, Department of Pediatrics
Department of Molecular Genetics and Microbiology
Duke Medical Center (US)
Corresponding author: Steinbach, William J.
ORCID: Steinbach, William J.
Cramer, Robert A.
Nielsen, Kirsten
Heitman, Joseph
Perfect, John R.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2007-08
Volume: 51
Issue: 8
Pages: 2979-2981
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.01394-06
PMC: PMC1932494
OpenAlex: W2143321217
Cited by: 108
References: 14
Citations by year: 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 12 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 8 · 2013: 3 · 2012: 6
FWCI: 7.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
BORIS (University Library Bern) (submittedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R56AI028388, AI28388, R01AI042159, R01AI42159, K08AI061149, R01AI028388, R01 AI50438, R01AI050438, T32AI052080)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords: calcineurin, calcineurin A, Aspergillus fumigatus, cell wall inhibitors, caspofungin, nikkomycin Z, β-1,3-glucan, antifungal therapy, adjunctive therapy, fungal cell wall
MeSH terms: Caspofungin, Aminoglycosides, Antifungal Agents, Aspergillus fumigatus, Cell Wall, Drug Synergism, Enzyme Inhibitors, Humans, Microbial Sensitivity Tests, Mutation, Peptides, Cyclic, Gene Expression Regulation, Fungal, Tacrolimus, Calcineurin, Echinocandins, Lipopeptides, Calcineurin Inhibitors

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Calcineurin Inhibition or Mutation Enhances Cell Wall Inhibitors against Aspergillus fumigatus

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