Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI) pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies.Keywords: cell wall integrity; mitogen-activated protein kinase (MAPK); signal transduction; transcription; gene expression; antifungal
Cell Wall Organization and Structure in S. cerevisiaeYeast cell integrity depends on the cell wall, an essential structure necessary not only for maintaining morphology but also for protecting cells against environmental stress conditions [1,2]. The cell wall is a macromolecular complex mainly composed of β-1,3-glucan, β-1,6-glucan, chitin and mannoproteins. Chitin, although a minor component, is essential for cell survival. β-1,3-glucan is the most abundant component of the yeast cell wall and serves as a backbone to which the other cell wall components are linked. The reducing ends of β-1,6-glucan and chitin are attached to the non-reducing end of β-1,3-glucan chains by an uncharacterized link and a β-1,4-linkage, respectively [3][4][5]. β-1,6-glucan is also attached to the chitin through β-1,3-linked oligogluco-residues that branch off the glucan. There is also a fraction of free chitin. Cell wall mannoproteins, including those involved in adhesion, cell wall remodeling, structural proteins and somatic antigens [6][7][8][9] can be linked directly to the β-1,3-glucan via alkali-labile bonds [9,10] and indirectly via β-1,6-glucan through a glycosylphosphatidylinositol (GPI) anchor [9,11]. The structure of the fungal cell wall is very well conserved among fungi despite several differences in cell wall composition exist [12]. Among fungal glucans, diversities in configuration, position of glyosidic bonds and branching have been reported [13]. β-1,3-glucan is the major cell wall component and is present in all the fungal species analyzed, whereas other polysaccharides including β-1,3/β-1,4-glucan, β-1,6-glucan or α-1,3-glucan a...