The Calcineurin‐Responsive Transcription Factor Crz1 Is Required for Conidation, Full Virulence and DMI Resistance in Penicillium Digitatum
Open accessAbstract
The Ca(2+)/calmodulin-dependent pathway is a critical signal transduction pathway that mediates various cellular responses in multiple organisms. Calcineurin acts through zinc finger transcription factor Crz1 in fungi. In the present study, we identified an ortholog of Crz1, PdCrz1, in Penicillium digitatum, the most important pathogen of postharvest citrus. To determine the function(s) of PdCrz1, a gene-disruption mutant was generated using an Agrobacterium tumefaciens-mediated transformation (ATMT) procedure. The PdCrz1 disruption (ΔPdCrz1) mutant was defective in conidiation, cell wall integrity and virulence, and was hypersensitivity to stresses caused by Ca(2+), H2O2 or 14α-demethylation inhibitor (DMI) fungicides. Expressions of cell wall synthase genes (CHS2, CHS3 and FKS1) and P-type ATPase genes (PMR1 and PMC1) were defective in the ΔPdCrz1 mutant when compared with the wild type. Calcineurin inhibitors were shown to enhance the effect of imazalil on P. digitatum. In contrast, Ca(2+) (≤0.2moll(-1)) could alleviate the antifungal activity by imazalil. These results indicate that PdCrz1 has important roles in conidiation, virulence and DMI resistance in P. digitatum. In addition, this study also indicates that specific calcium signaling pathway inhibitors could be used as adjuvants in the conventional DMI fungicides.
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Within the up-regulated 248-gene set, several genes known to be regulated by the calcineurin/Crz1 pathway, including CHS3, UTR2, ALG5, etc., showed significant upregulation with increasing caspofungin concentration.
“Notably, within the up‐regulated 248‐gene, we identified several genes known to be regulated by the calcineurin/Crz1 pathway, including CHS3 (encoding chitin synthase III), UTR2, ALG5, etc., which showed significant upregulation with increasing caspofungin concentration [24, 25].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in <i>Candida Glabrata</i> (2026) · cites this paper as [24]
The section ‘PdCrz1 affects expression of calcineurin-dependent genes’ reports that CHS3 expression increased with CaCl2 treatment in wild-type Penicillium digitatum but not in the PdCrz1 mutant, supporting CHS3 as a pathway-regulated example. Our copy does not establish that UTR2 or ALG5 are regulated by this pathway. The 248-gene set and caspofungin response are presented as the citing authors’ own findings, not findings attributed to this source. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCHS3 expression depends on Crz1 under Ca2+ stress, and its disruption leads to cell wall integrity defects.
“CHS3 expression has been shown to depend on Crz1 under Ca2 + stress, and its disruption leads to cell wall integrity defects [24].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in <i>Candida Glabrata</i> (2026) · cites this paper as [24]
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References 45 · Cited by 75
Research works printed but not linked: 3
- Hernandez-Lopez MJ, Panadero J, Prieto JA, Randez-Gil F. Regulation of salt tolerance by Torulaspora delbrueckii calcineurin target Crz1p. Eukaryot Cell 2006;5(3):469-79.
- Tang QY, Feng MG. DPS data processing system: experimental design, statistical analysis and data mining. Beijing, China: Science Press; 2007.
- Wiesenberger G, Steinleitner K, Malli R, Graier WF, Vormann J, Schweyen RJ, et al. Mg 2+ deprivation elicits rapid Ca 2+ uptake and activates Ca 2+ /calcineurin signaling in Saccharomyces cerevisiae. Eukaryot Cell 2007;6(4):592-9.
- Authors
- Zhang, T., Xu, Q., Sun, X., & Li, H.
- Affiliations
- Zhejiang University (CN)
- Corresponding author
- Li, Hongye
- Venue
- Microbiological Research
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 168
- Issue
- 4
- Pages
- 211-222
- ISSN
- 0944-5013 (ISSN-L)
- OpenAlex
- W2038157212
- Cited by
- 75
- References
- 45
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 8 · 2015: 2 · 2014: 7 · 2013: 1
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Microbiological Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Foundation of Natural Science of China (31071649)
- Modern Agro-industry Technology Research System (MATRS)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Plant Pathogens and Fungal Diseases
- Keywords
- Crz1, calcineurin, Penicillium digitatum, conidiation, fungal virulence, imazalil, calcium signaling, cell wall integrity, P-type ATPase, fungicide adjuvants, gene disruption mutants
- MeSH terms
- Citrus, Fungal Proteins, Fungicides, Industrial, Penicillium, Plant Diseases, Spores, Fungal, Transcription Factors, Virulence, Gene Expression Regulation, Fungal, Calcineurin, Drug Resistance, Fungal
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