Fungal cell wall integrity pathway (CWI pathway)

The fungal cell wall integrity (CWI) pathway is a conserved signaling cascade in fungi that regulates the synthesis and remodeling of the cell wall in response to environmental stresses, antifungal drugs, and morphogenesis. At the core of this pathway is a MAPK cascade initiated by extracellular stress sensors, which signal through GTPases and kinases (notably protein kinase C, Pkc1) to downstream MAPK modules (such as Bck1-Mkk1/2-Slt2 in yeast), regulating the expression of enzymes responsible for wall biosynthesis (e.g., β-1,3-glucan synthase, chitin synthase) and morphogenetic factors. Disruption of this signaling impairs fungal survival, makes the cell wall vulnerable, and underpins the mechanism of action of major antifungal drugs (like echinocandins). As the cell wall is essential and absent in host animals, the pathway and its molecular components are primary antifungal targets, though its complexity and compensatory signaling can lead to therapeutic resistance[1][3][4][6][9].\n\nIn summary, "Fungal cell wall integrity" is a process and signaling pathway, not a single druggable receptor or protein, though its molecular constituents (e.g., β-1,3-glucan synthase, pathway kinases) are proven, specific antifungal drug targets.

Other names

Cell wall integrity pathwayCWI pathwayfungal CWI pathway

Inhibition of β-1,3-glucan synthase (disrupts glucan synthesis, weakens wall, causes lysis)\nInhibition of GPI-anchor biosynthesis (hinders cell wall protein anchoring)\nDisruption of cell wall assembly and stress signaling cascade