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• W2116721311 abstract "ABSTRACT The interaction between Candida albicans and cells of the innate immune system is a key determinant of disease progression. Transcriptional profiling has revealed that C. albicans has a complex response to phagocytosis, much of which is similar to carbon starvation. This suggests that nutrient limitation is a significant stress in vivo, and we have shown that glyoxylate cycle mutants are less virulent in mice. To examine whether other aspects of carbon metabolism are important in vivo during an infection, we have constructed strains lacking FOX2 and FBP1 , which encode key components of fatty acid β-oxidation and gluconeogenesis, respectively. As expected, fox2 Δ mutants failed to utilize several fatty acids as carbon sources. Surprisingly, however, these mutants also failed to grow in the presence of several other carbon sources, whose assimilation is independent of β-oxidation, including ethanol and citric acid. Mutants lacking the glyoxylate enzyme ICL1 also had more severe carbon utilization phenotypes than were expected. These results suggest that the regulation of alternative carbon metabolism in C. albicans is significantly different from that in other fungi. In vivo, fox2 Δ mutants show a moderate but significant reduction in virulence in a mouse model of disseminated candidiasis, while disruption of the glyoxylate cycle or gluconeogenesis confers a severe attenuation in this model. These data indicate that C. albicans often encounters carbon-poor conditions during growth in the host and that the ability to efficiently utilize multiple nonfermentable carbon sources is a virulence determinant. Consistent with this in vivo requirement, C. albicans uniquely regulates carbon metabolism in a more integrated manner than in Saccharomyces cerevisiae , such that defects in one part of the machinery have wider impacts than expected. These aspects of alternative carbon metabolism may then be useful as targets for therapeutic intervention." @default.
• W2116721311 created "2016-06-24" @default.
• W2116721311 creator A5046450698 @default.
• W2116721311 creator A5076041024 @default.
• W2116721311 date "2007-02-01" @default.
• W2116721311 modified "2023-10-16" @default.
• W2116721311 title "Mutations in Alternative Carbon Utilization Pathways in <i>Candida albicans</i> Attenuate Virulence and Confer Pleiotropic Phenotypes" @default.
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• W2116721311 doi "https://doi.org/10.1128/ec.00372-06" @default.
• W2116721311 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1797957" @default.
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