EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays

Abstract

SummaryCell wall dynamics in Candida albicans , the most common fungal pathogen in man, underlie regulatory processes during the yeast-to-hyphae transition. To analyse this regulation at the transcriptional level, we have established a DNA microarray representing genes implicated in cell wall biogenesis. Using these microarrays, we were able to identify YWP1 and HWP2 that are specifically transcribed in the yeast or hyphal growth form respectively. Cluster analysis revealed at least two major clusters of genes: cluster I comprised genes that were upregulated under at least one hyphae-inducing condition. Three as yet not further characterized genes were attributed to cluster II. These genes were transcribed in the yeast form of C. albicans and were downregulated in an EFG1 -dependent manner under specific hyphae-inducing conditions. We show further that, in contrast to CPH1 , EFG1 plays a major role in the transcriptional regulation of cell wall proteins under the conditions investigated. EFG1 was essential for the transcription of both hyphae-specific genes such as HWP1 and HWP2 as well as the yeast form-specific gene YWP1 . Moreover, we found that, under various conditions, EFG1 also can act as a strong repressor for the transcription of RBE1 , another not yet characterized cell wall protein. Overall, our data show that EFG1 plays a major role in the induction and repression of cell wall genes, not only in the hyphal form but also in the yeast form of C. albicans .

Deletion of PDE2, the gene encoding the high‐affinity cAMP phosphodiesterase, results in changes of the cell wall and membrane in Candida albicans

“…Changes in expression of cell wall-related genes and associated cell wall defects have previously been demonstrated in S. cerevisiae pde2 mutants (Jones et al, 2003). Our results suggest that a similar effect might also exist in C. albicans, since recent reports have demonstrated, first, that EFG1 is significantly downregulated in the C.albicans pde2 mutant (Jung and Stateva, 2003) and second, that EFG1 regulates transcription of several cell wall proteinencoding genes such as HWP1, HWP2, YWP1 and RBE1, which are significantly downregulated in an efg1 mutant (Sohn et al, 2003). The structural differences of the cell wall in the homozygous pde2 mutant were demonstrated using biochemical analysis and transmission electron microscopy.…”

Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation inCandida albicans

“…Hyphaspecific genes are not the only genes affected in efg1 mutants as determined by genome-wide transcription analyses (Sohn et al, 2003;Doedt et al, 2004;Harcus et al, 2004;Cao et al, 2006;Setiadi et al, 2006), and Efg1 also regulates other cellular processes and development (Lo et al, 1997;Stoldt et al, 1997;Sonneborn et al, 1999;Srikantha et al, 2000;Zordan et al, 2007). Phd1, a member of the APSES family in S. cerevisiae, binds to DNA nonspecifically in vitro (Ho et al, 2006), but it binds specific promoters in vivo (Borneman et al, 2006); therefore, Phd1 is thought to use additional cofactors to achieve sequence-specific binding in yeast (Ho et al, 2006).…”

“…It is suggested to function downstream of the cAMP/protein kinase A (PKA) pathway in hyphal development (Sonneborn et al, 2000;Bockmuhl and Ernst, 2001), and both Efg1 and PKA are required for the induction of hypha-specific genes. However, Efg1 also regulates other genes that are not modulated by the cAMP pathway (Sohn et al, 2003;Doedt et al, 2004;Harcus et al, 2004;Setiadi et al, 2006). Numerous in vitro and in vivo studies with efg1 mutants have demonstrated that Efg1 is important for C. albicans virulence and for the interactions of C. albicans with endothelial and epithelia cells, as well as biofilm formation and catheter infection (Lo et al, 1997;Phan et al, 2000;Dieterich et al, 2002;Lewis et al, 2002;Ramage et al, 2002;Garcia-Sanchez et al, 2004).…”

Niche-specific gene expression during C. albicans infection

“…While numerous transcription factors are needed for full virulence of C. albicans, their roles in gene expression in different host niches are not known. For example, the well studied transcription factor Efg1p, is required for expression of SAP5, ECE1, RBT1, RBT4 and other hypha-coregulated genes during growth of cells in laboratory conditions [24,25,[40][41][42]. However, Efg1p is not required for expression of ECE1, RBT1 or RBT4 during commensal colonization of the murine intestinal tract [32].…”