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Cited by 159Fungal and yeast genetics researchBacterial Genetics and BiotechnologyAntifungal resistance and susceptibility

Candida albicans Response Regulator Gene SSK1 Regulates a Subset of Genes Whose Functions Are Associated with Cell Wall Biosynthesis and Adaptation to Oxidative Stress

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Chauhan, Neeraj, Inglis, Diane, Roman, Elvira, Pla, Jesus, Li, Dongmei, Calera, Jose A., Calderone, Richard·2003·Eukaryotic Cell
DOI 10.1128/ec.2.5.1018-1024.2003PMC PMC219380
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Abstract

Ssk1p of Candida albicans is a putative response regulator protein of the Hog1 two-component signal transduction system. In Saccharomyces cerevisiae, the phosphorylation state of Ssk1p determines whether genes that promote the adaptation of cells to osmotic stress are activated. We have previously shown that C. albicans SSK1 does not complement the ssk1 mutant of S. cerevisiae and that the ssk1 mutant of C. albicans is not sensitive to sorbitol. In this study, we show that the C. albicans ssk1 mutant is sensitive to several oxidants, including hydrogen peroxide,t-butyl hydroperoxide, menadione, and potassium superoxide when each is incorporated in yeast extract-peptone-dextrose (YPD) agar medium. We used DNA microarrays to identify genes whose regulation is affected by the ssk1 mutation. RNA from mutant cells (strain CSSK21) grown in YPD medium for 3 h at 30°C was reverse transcribed and then compared with similarly prepared RNA from wild-type cells (CAF2). We observed seven genes from mutant cells that were consistently up regulated (three-fold or greater compared to CAF2). In S. cerevisiae, three (AHP1,HSP12, and PYC2) of the seven genes that were up regulated provide cells with an adaptation function in response to oxidative stress; another gene (GPH1) is regulated under stress conditions by Hog1p. Three other genes that are up regulated encode a cell surface protein (FLO1), a mannosyl transferase (MNN4-4), and a putative two-component histidine kinase (CHK1) that regulates cell wall biosynthesis in C. albicans. Of the down-regulated genes,ALS1 is a known cell adhesin in C. albicans. Verification of the microarray data was obtained by reverse transcription-PCR for HSP12,AHP1,CHK1,PYC2,GPH1,ALS1,MNN4-4, and FLO1. To further determine the function of Ssk1p in the Hog1p signal transduction pathway in C. albicans, we used Western blot analysis to measure phosphorylation of Hog1p in the ssk1 mutant of C. albicans when grown under either osmotic or oxidative stress. We observed that Hog1p was phosphorylated in the ssk1 mutant of C. albicans when grown in a hyperosmotic medium but was not phosphorylated in the ssk1 mutant when the latter was grown in the presence of hydrogen peroxide. These data indicate that C. albicans utilizes the Ssk1p response regulator protein to adapt cells to oxidative stress, while its role in the adaptation to osmotic stress is less certain. Further,SSK1 appears to have a regulatory function in some aspects of cell wall biosynthesis. Thus, the functions of C. albicans SSK1 differ from those of S. cerevisiae SSK1.

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Crossref · 10.1128/ec.2.5.1018-1024.2003

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  • Ahp1 is a member of the peroxiredoxin family and cooperates with other peroxidases such as Trx1 to protect cells from ROS.

    “Ahp1 is a member of the peroxiredoxin family, cooperates with other peroxidase such as Trx1 to protect cells from ROS [69].”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [69]

  • Ahp1 plays a pivotal role in the formation of AmB-tolerant C. albicans biofilm persisters.

    “Furthermore, another anti-oxidative stress enzyme, alkyl hydroperoxide reductase 1 (Ahp1), was found to play a pivotal role in the formation of AmB-tolerant C. albicans biofilm persisters.”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [69]

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Authors
Chauhan, N., Inglis, D., Roman, E., Pla, J., Li, D., Calera, J. A., & Calderone, R.
Affiliations
  • Georgetown University (US)
  • University of California, San Francisco (US)
  • Departamento de Microbiología II, Universidad Complutense de Madrid, Madrid
  • Departamento de Microbiología, Universidad de Salamanca, Salamanca, Spain
Corresponding author
Calderone, Richard
ORCID
Venue
Eukaryotic Cell
Publisher
American Society for Microbiology
Published
2003-10
Volume
2
Issue
5
Pages
1018-1024
ISSN
  • 1535-9778 (ISSN-L)
  • 1535-9786
DOI
10.1128/ec.2.5.1018-1024.2003
PMC
PMC219380
OpenAlex
W2154156375
Cited by
159
References
53
Citations by year
2025: 8 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 8 · 2018: 3 · 2017: 9 · 2016: 9 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 4
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Eukaryotic Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Rutgers University Community Repository (Rutgers University) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R01AI049187, R01AI043465, AI43465, R01 AI 49187, AI 47047, R01AI047047)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords
Candida albicans, oxidative stress response, cell wall biosynthesis, gene expression regulation, osmotic stress, HSP12, FLO1, Chk1, ALS1, stress adaptation, DNA microarrays
MeSH terms
Adaptation, Physiological, Candida albicans, Cell Division, Cell Wall, Dose-Response Relationship, Drug, Fungal Proteins, Genes, Regulator, Hydrogen Peroxide, Mutation, Phosphorylation, Sodium Chloride, Superoxides, Down-Regulation, Up-Regulation, Gene Expression Regulation, Fungal, Gene Deletion, Oxidative Stress, Heat-Shock Response, tert-Butylhydroperoxide, Oligonucleotide Array Sequence Analysis, Mitogen-Activated Protein Kinases, Vitamin K 3

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