The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function
Open accessAbstract
Summary: Cell wall integrity is crucial for fungal growth, development and stress survival. In the model yeast Saccharomyces cerevisiae, the cell integrity Mpk1/Slt2 MAP kinase and calcineurin pathways monitor cell wall integrity and promote cell wall remodelling under stress conditions. We have identified the Cryptococcus neoformans homologue of the S. cerevisiae Mpk1/Slt2 MAP kinase and have characterized its role in the maintenance of cell integrity in response to elevated growth temperature and in the presence of cell wall synthesis inhibitors. C. neoformans Mpk1 is required for growth at 37°C in vitro, and this growth defect is suppressed by osmotic stabilization. C. neoformans mutants lacking Mpk1 are attenuated for virulence in the mouse model of cryptococcosis. Phosphorylation of Mpk1 is induced in response to perturbations of cell wall biosynthesis by the antifungal drugs nikkomycin Z (a chitin synthase inhibitor), caspofungin (a β‐1,3‐glucan synthase inhibitor), or FK506 (a calcineurin inhibitor), and mutants lacking Mpk1 display enhanced sensitivity to nikkomycin Z and caspofungin. Lastly, we show that calcineurin and Mpk1 play complementing roles in regulating cell integrity in C. neoformans. Our studies demonstrate that pharmacological inhibition of the cell integrity pathway would enhance the activity of antifungal drugs that target the cell wall.
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“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 Candida glabrata (2010) · cites this paper as [18]
In the citing paper
“Although the C. albicans cnb1 mutant strain showed filamentous growth in vivo, it failed to grow in a mouse model of disseminated candidiasis and was unable to survive in serum, revealing evolutionarily distinct control aspects of calcineurin over virulence of two divergent fungal pathogens via distinct mechanisms (Blankenship and Heitman, 2005; Blankenship et al., 2003; Kraus et al., 2003).”
From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Kraus et al., 2003
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Regulatory circuitry governing fungal development, drug resistance, and disease.
Shapiro, R. S., Robbins, N., & Cowen, L. E. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00045-10 · Cited by 576
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Stimulation of Chitin Synthesis Rescues Candida albicans from Echinocandins
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Mitogen-Activated Protein Kinase Pathways and Fungal Pathogenesis
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Metadata
- Authors
- Kraus, P. R., Fox, D. S., Cox, G. M., & Heitman, J.
- Affiliations
- Duke Medical Center (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Heitman, Joseph
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2003-04-29
- Volume
- 48
- Issue
- 5
- Pages
- 1377-1387
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1586693095
- Cited by
- 217
- References
- 56
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 8 · 2018: 11 · 2017: 11 · 2016: 18 · 2015: 7 · 2014: 13 · 2013: 10 · 2012: 6
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases (R37AI039115, P01-AI44975, R01AI042159, R01 AI39115, R01AI42159, P01AI044975, R01 AI50438, R01AI050438, R01AI039115)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Cryptococcus neoformans, Mpk1, cell integrity pathway, calcineurin, antifungal resistance, nikkomycin Z, caspofungin, FK506, chitin synthase inhibition, cell wall integrity, osmotic stabilization, virulence, cryptococcosis, drug synergy
- MeSH terms
- Animals, Antifungal Agents, Cell Wall, Cryptococcosis, Cryptococcus neoformans, Culture Media, Enzyme Inhibitors, Female, Fungal Proteins, Mice, Inbred DBA, Temperature, Virulence, Gene Expression Regulation, Fungal, Calcineurin, Mitogen-Activated Protein Kinases, Saccharomyces cerevisiae Proteins, Mice, Calcineurin Inhibitors
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