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

Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
Infection and immunity (Impact Factor: 3.73). 07/2008; 76(6):2793-801. DOI: 10.1128/IAI.01514-07
Source: PubMed


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 ino1Δ/ino1Δ mutant was an inositol auxotroph, and the itr1Δ/itr1Δ 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 ino1Δ/ino1Δ itr1Δ/itr1Δ 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 ino1Δ/ino1Δ itr1Δ/ITR1 strain with a conditionally expressed allele of ITR1 driven by the repressible MET3 promoter. The resulting ino1Δ/ino1Δ itr1Δ/PMET3::ITR1 strain was found to be nonviable in medium containing methionine and cysteine (which represses the PMET3 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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Available from: Todd Reynolds, Nov 21, 2014
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    • "This appears to be true for C. albicans in the host as well, since in a mouse model for systemic infection, the conditional double mutant was avirulent and the mice showed no symptoms of infection, which is consistent with the hypothesis that the strains could not survive due to a lack of inositol. The mouse bloodstream contains sufficient Cys/Met to shut off the P MET3 promoter (Chen et al., 2008; Rodaki et al., 2006). Even a strain that contained homozygous mutations for CaINO1 and was heterozygous for CaITR1 was attenuated for virulence compared to the wild-type, although it was more virulent than the conditional double mutant. "
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