Stress adaptation in a pathogenic fungus
Open accessAbstract
Candida albicans is a major fungal pathogen of humans. This yeast is carried by many individuals as a harmless commensal, but when immune defences are perturbed it causes mucosal infections (thrush). Additionally, when the immune system becomes severely compromised, C. albicans often causes life-threatening systemic infections. A battery of virulence factors and fitness attributes promote the pathogenicity of C. albicans. Fitness attributes include robust responses to local environmental stresses, the inactivation of which attenuates virulence. Stress signalling pathways in C. albicans include evolutionarily conserved modules. However, there has been rewiring of some stress regulatory circuitry such that the roles of a number of regulators in C. albicans have diverged relative to the benign model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. This reflects the specific evolution of C. albicans as an opportunistic pathogen obligately associated with warm-blooded animals, compared with other yeasts that are found across diverse environmental niches. Our understanding of C. albicans stress signalling is based primarily on the in vitro responses of glucose-grown cells to individual stresses. However, in vivo this pathogen occupies complex and dynamic host niches characterised by alternative carbon sources and simultaneous exposure to combinations of stresses (rather than individual stresses). It has become apparent that changes in carbon source strongly influence stress resistance, and that some combinatorial stresses exert non-additive effects upon C. albicans. These effects, which are relevant to fungus–host interactions during disease progression, are mediated by multiple mechanisms that include signalling and chemical crosstalk, stress pathway interference and a biological transistor.
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In vitro conditions that mimic the host microenvironment at the infection site can cause yeast cells to develop wall modifications and antifungal resistance.
“In vitro studies have shown in conditions that mimic the host microenvironment at the infection site that yeast cells may develop wall modifications and antifungal resistance (Ene et al., 2012; Brown et al., 2014).”
From Fungal Cell Wall: Emerging Antifungals and Drug Resistance. (2019) · cites this paper as Brown et al., 2014
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Thioredoxin Regulates Multiple Hydrogen Peroxide-Induced Signaling Pathways in Candida albicans
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A Single MAPKKK Regulates the Hog1 MAPK Pathway in the Pathogenic Fungus Candida albicans
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Self-citationThe Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans
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Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of <i>Candida albicans</i>
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CTA4 Transcription Factor Mediates Induction of Nitrosative Stress Response in Candida albicans
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- Authors
- Brown, A. J. P., Budge, S., Kaloriti, D., Tillmann, A., Jacobsen, M. D., Yin, Z., Ene, I. V., Bohovych, I., Sandai, D., Kastora, S., Potrykus, J., Ballou, E. R., Childers, D. S., Shahana, S., & Leach, M. D.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Brown, Alistair J. P.
- ORCID
- Venue
- Journal of Experimental Biology
- Publisher
- The Company of Biologists
- Published
- 2014-01-01
- Volume
- 217
- Issue
- 1
- Pages
- 144-155
- ISSN
- 0022-0949 (ISSN-L)
- 1477-9145
- PMC
- PMC3867497
- OpenAlex
- W2166216188
- Cited by
- 299
- References
- 157
- Citations by year
- 2026: 34 · 2025: 26 · 2024: 17 · 2023: 17 · 2022: 29 · 2021: 24 · 2020: 30 · 2019: 19 · 2018: 15 · 2017: 31 · 2016: 34 · 2015: 16 · 2014: 7
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Experimental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (097377/Z/11/Z, 097377, 096072, 080088)
- Biotechnology and Biological Sciences Research Council (BB/D009308/1, BBS/B/06679, BB/C510391/1, BB/F000111/1, BB/K017365/1, BB/F00513X/1, BB/F010826/1)
- 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 › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Candida albicans, stress adaptation, virulence factors, opportunistic fungal pathogens, carbon source regulation, Saccharomyces cerevisiae, Schizosaccharomyces pombe, host-pathogen interaction
- MeSH terms
- Adaptation, Physiological, Candida albicans, Fungal Proteins, Glucose, Osmotic Pressure, Saccharomyces cerevisiae, Schizosaccharomyces, Signal Transduction, Oxidative Stress, Heat-Shock Response, Mitogen-Activated Protein Kinases
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