Candida albicans Uses Multiple Mechanisms To Acquire the Essential Metabolite Inositol during Infection
Open accessAbstract
Candida albicans is an important cause of life-threatening systemic bloodstream infections in immunocompromised patients. In order to cause infections, C. albicans must be able to synthesize the essential metabolite inositol or acquire it from the host. Based on the similarity of C. albicans to Saccharomyces cerevisiae, it was predicted that C. albicans may generate inositol de novo, import it from the environment, or both. The C. albicans inositol synthesis gene INO1 (orf19.7585) and inositol transporter gene ITR1 (orf19.3526) were each disrupted. The ino1Delta/ino1Delta mutant was an inositol auxotroph, and the itr1Delta/itr1Delta mutant was unable to import inositol from the medium. Each of these mutants was fully virulent in a mouse model of systemic infection. It was not possible to generate an ino1Delta/ino1Delta itr1Delta/itr1Delta double mutant, suggesting that in the absence of these two genes, C. albicans could not acquire inositol and was nonviable. A conditional double mutant was created by replacing the remaining wild-type allele of ITR1 in an ino1Delta/ino1Delta itr1Delta/ITR1 strain with a conditionally expressed allele of ITR1 driven by the repressible MET3 promoter. The resulting ino1Delta/ino1Delta itr1Delta/P(MET3)::ITR1 strain was found to be nonviable in medium containing methionine and cysteine (which represses the P(MET3) promoter), and it was avirulent in the mouse model of systemic candidiasis. These results suggest a model in which C. albicans has two equally effective mechanisms for obtaining inositol while in the host. It can either generate inositol de novo through Ino1p, or it can import it from the host through Itr1p.
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Methionine levels in the mouse are sufficient to repress gene expression from the MET3 promoter in C. albicans leading to avirulence of conditional mutants.
“Methionine levels in the mouse are sufficient to repress gene expression from the MET3 promoter in C. albicans leading to avirulence of conditional mutants [105], allowing us to test fungal burden of mice infected with the MET3p-HSP90 strain.”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [105]
The Results report that the conditional MET3-promoter ITR1 strains were avirulent in mice. But the Discussion says methionine and cysteine in mouse serum are *apparently* sufficient to decrease promoter expression; it does not establish that mouse methionine levels alone cause the avirulence asserted in the claim. Page numbers were not provided in our copy. (LLM, conf=0.83)
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- Authors
- Chen, Y.-L., Kauffman, S., & Reynolds, T. B.
- Affiliations
- University of Tennessee at Knoxville (US)
- Corresponding author
- Reynolds, Todd B.
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2008-06
- Volume
- 76
- Issue
- 6
- Pages
- 2793-2801
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC2423082
- OpenAlex
- W2168393075
- Cited by
- 47
- References
- 44
- Citations by year
- 2026: 4 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 7 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 7
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R03AI071863)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida albicans, auxotrophy, virulence, systemic candidiasis, host-pathogen interaction, conditional gene expression
- MeSH terms
- Animals, Candida albicans, Candidiasis, Carrier Proteins, Fungal Proteins, Inositol, Male, Mutation, Virulence, Gene Expression Regulation, Fungal, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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