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. 2019 Oct 30;5(4):102.
doi: 10.3390/jof5040102.

Genetic Regulators and Physiological Significance of Glycogen Storage in Candida albicans

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Free PMC article

Genetic Regulators and Physiological Significance of Glycogen Storage in Candida albicans

Marcus A Zeitz et al. J Fungi (Basel). .
Free PMC article

Abstract

The dimorphic human fungal pathogen C. albicans has broad metabolic flexibility that allows it to adapt to the nutrient conditions in different host habitats. C. albicans builds large carbohydrate stores (glycogen) at the end of exponential growth and begins consumption of stored carbohydrates when nutrients become limiting. The expression of genes required for the successful transition between host environments, including the factors controlling glycogen content, is controlled by protein kinase A signaling through the transcription factor Efg1. In addition to the inability to transition to hyphal growth, C. albicans efg1 mutants have low glycogen content and reduced long-term survival, suggesting that carbohydrate storage is required for viability during prolonged culture. To test this assumption, we constructed a glycogen-deficient C. albicans mutant and assessed its viability during extended culture. Pathways and additional genetic factors controlling C. albicans glycogen synthesis were identified through the screening of mutant libraries for strains with low glycogen content. Finally, a part of the Efg1-regulon was screened for mutants with a shortened long-term survival phenotype. We found that glycogen deficiency does not affect long-term survival, growth, metabolic flexibility or morphology of C. albicans. We conclude that glycogen is not an important contributor to C. albicans fitness.

Keywords: Candida albicans; Efg1; glycogen; glycogen synthase GSY1.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Glycogen content and viability of C. albicans wildtype (WT) SN152 and corresponding efg1/efg1 mutant. (a) Glycogen content of WT reaches a low after 10 days of culture on YPD media. Viability declines around day 10 of culture. efg1 null mutants have a low glycogen content from the start and viability declines more rapidly than in the WT; (b) Validation of a mechanical isolation assay to assess viability of cultures, confirming loss of viability at day 16 (WT) and 12 (efg1/efg1). (c) Viability of efg1/efg1 mutant on a variety of solid media. In each case, the difference between WT and mutant is significant (p < 0.05).
Figure 2
Figure 2
Glycogen content of WT, heterozygous and homozygous glycogen synthase mutants in exponential (6 h) and stationary (48 h) phase of growth. Glycogen content of three independent gsy1/gsy1 isolates is shown. The difference in glycogen content between WT and gsy1/gsy1 mutant is significant at the 5% level.
Figure 3
Figure 3
Glycogen content of efg1/efg1 and tup1/tup1 mutants from Homan et al. library assessed with the iodine vapor method. Ten microliters of a stationary culture were grown for 6 h on YPD plates and exposed to iodine vapor for 15 min (in duplicate). The intensity of brown coloration is a measure of glycogen content (efg1/efg1: low; tup1/tup1: high).

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