Role of Yeast Casein Kinase 2 in Morphogenesis, Biofilm Formation, Cell Wall Integrity and Host Cell Damage of Candida Albicans

Yeast casein kinase 2 governs morphology, biofilm formation, cell wall integrity, and host cell damage of Candida albicans

Jung et al. (1) did an investigation of Yeast casein kinase 2 (CaYck2p) function on Candida albicans. The ability of C. albicans

to switch morphologies in different host environments is an important virulent feature. The authors generated and investigated yck2Δ/yck2Δ homozygous strain whose YCK2 protein coding region was removed. The findings showed that in C. albicans, Yck2p governs morphogenesis, the formation of biofilm, the integrity of cell wall as well as the interactions of host cell.

In Figure 1A, it is shown that the transcript levels of YCK3 went up, but those of HRR25 remained constant in the yck2Δ/yck2Δ train than in the wild-type strain as well as the complement strain of yck2Δ/yck2Δ+YCK2. In Figure 1B, the colony morphology of the different strains has been portrayed to be very different as the wild-type strain is shown to have formed smooth convex colonies on YPD agar at 30°C. The main question for discussion would be to find out why there were differences in the colony morphology. Figure 1C shows growth differences in the varying strains as yck2Δ/yck2Δ strain is shown to have grown as chains of long yeast cells in the two different mediums, which could be attributed to the absence of functional YCK2 alleles. Figure 2A shows the extent of biofilm formation by yck2Δ/yck2Δ strain in different conditions. The strain is shown to have formed notably increased biofilm in the two conditions than the wild-type strain. It would be very important to explain the noted difference between the wild-type strain and yck2Δ/yck2Δ strain as far as biofilm formation is concerned. In figure 2B, yck2Δ/yck2Δ strain continues to form increased biofilm compared to the wild-type strain in YPGly at 37°C, a non-biofilm inducing condition for the wild-type, which is an important finding that suggests the enhanced capacity of yck2Δ/yck2Δ strain to form biofilms in conditions that do not favour biofilm formation by the wild-type. Figure 2C shows the importance of Yck2p in normal cell damage by the fungi C. albicans. Unlike the wild-type strain, the yck2Δ/yck2Δ strain caused less damage to the host cells used because of the removed YCK2 copy. Therefore, this is a clear indication that CaYck2p is needed to destroy epithelial and endothelial cells invivo. In Figure 3A, the importance of YCK2 has been demonstrated to govern the integrity of cell wall. While yck2Δ/yck2Δ strain showed that CaYck2p is not needed to make it resistant to osmotic and oxidative stress, yck2Δ/yck2Δ strain showed that it was susceptible. The main question for discussion should be aimed at understanding why CaYck2p is not related to osmotic or oxidative stress response, but governs the integrity of cell wall. Table 1 illustrates the degree of hypersensitivity of the strains to stressors of cell wall using the MIC values of fluconazole and caspofungin, which showed that yck2Δ/yck2Δ strain, was hyper-susceptible than the wild-strain and other strains.

To identify the possible regulatory mechanism used by CaYck2p to maintain cell wall integrity, Figure 3B show that yck2Δ/yck2Δ strain grew like the wild-type strain to suggest that Yck2p does not affect the integrity of cell wall through calcinerium pathway. Figure 3C, 4A, and 4B shows that loss of Yck2p induces compensatory synthesis of chitin. Absence of functional CaYck2p increases chitin synthesis. Figure 5 entails quantitative gene expression analysis with an aim of elucidating the molecular mechanisms of the changed phenotype of yck2Δ/yck2Δ strain by measuring BCR1, CPH1, and EFG1 expression levels involved in hyphal transition and formation of biofilm. Based on Figure 5A the increased UME6 expression in the yck2Δ/yck2Δ strain could lead to pseudohyphal growth and formation of increased biofilm under conditions inducing yeast. Based on Figure 5B, CaYck2p has no involvement in transcriptional regulation of the genes.

Works Cited

Jung, Sook-In, Natalie Rodriguez, Jihyun Irrizary, Karl Liboro, Thania Bogarin, Marlene Macias, Edward Eivers, Edith Porter, Scott G. Filler, and Hyunsook Park. “Yeast casein kinase 2 governs morphology, biofilm formation, cell wall integrity, and host cell damage of Candida albicans.” PloS one 12.11 (2017): e0187721.