Cited by 47Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

Candida albicans Uses Multiple Mechanisms To Acquire the Essential Metabolite Inositol during Infection

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Chen, Ying-Lien, Kauffman, Sarah, Reynolds, Todd B.·2008·Infection and Immunity

Abstract

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
Published
2008-06
Volume
76
Issue
6
Pages
2793-2801
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
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
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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