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Physiological adaptations in Candida albicans
Candida albicans is the most important fungal pathogen of human, with a remarkable ability to withstand constantly changing microenvironment within the host through its morphological and metabolic plasticity. These fine-tuning mechanisms based on the ecological niche enhance its pathogenic potential and increase its fitness. Our understanding of what, when and how these mechanisms and factors contribute to commensal and pathogenic C. albicans is still insufficient for the development of efficient drugs against C. albicans infections. This dissertation addresses unique biological aspects evolved to increase the fitness attributes of C. albicans using both in vitro and in vivo studies. First, we investigate the in vitro and in vivo role of chlamydospores using a previously identified chlamydospore defective mutant Δisw2/Δisw2. We found that chlamydospores can be produced by C. albicans during mouse kidney colonization and ISW2 (orf19.7401) regulates suspensor cell formation rather than the spore itself. Screening for nutritional triggers for induction of chlamydospores suggests that these are formed as a response to nutritional stress rather than being a reproductive mode or resting stage. Secondly, we characterized FMS1 (orf19.4589) and CBP1 (orf19.7323), the two genes predicted to be rate limiting in pantothenic acid biosynthesis in yeasts. This is the first study to use gene deletion mutants to characterize their function and our findings indicate C. albicans has redundant roles for FMS1 compared to its ortholog in Sachcharomyces cerevisiae. Our findings fortuitously identified a ‘novel’ histidine biosynthesis regulatory pathway in Candida biology. This study illuminates novel metabolic switching circuitry through which C. albicans fulfil its essential primary metabolites. Thirdly, we investigated why C. albicans and C. dubliniensis evolved to use ubiquinone 9 (UQ9) rather than ubiquinone 7 (UQ7) as in other Candida species. We have shown that the presence of longer isoprenoid chains aids farnesol tolerance by comparing the farnesol sensitivity of S. cerevisiae (UQ6) with that of a strain modified to produce UQ9. Here we propose the presence of UQ9 is a physiological adaptation for stress tolerance in this pathogenic yeast.
Pathirana, Ruvini U, "Physiological adaptations in Candida albicans" (2016). ETD collection for University of Nebraska - Lincoln. AAI10245264.