Microbial cell wall integrity pathway (CWI pathway)

The microbial cell wall integrity pathway (often abbreviated as CWI or cell wall integrity signaling pathway) is a conserved signal transduction network central to maintaining the structure and function of the cell wall in fungi and certain other microorganisms[1][2][4][5]. This pathway coordinates the biosynthesis and remodeling of key cell wall components—such as β-glucans, chitin, and mannoproteins—in response to various types of cellular stress, including those induced by antifungal drugs, oxidative challenges, and changes in osmotic pressure[1][4][5]. The pathway consists of cell surface sensors (e.g., Wsc1, Mid2), which detect perturbations in cell wall or membrane integrity and activate small GTPases (e.g., Rho1), leading to activation of protein kinase C (Pkc1) and a mitogen-activated protein kinase (MAPK) cascade (typically Bck1 → Mkk1/2 → Slt2/Mpk1)[1][2][3][4][5]. Ultimately, this results in the phosphorylation of transcription factors that orchestrate the expression of cell wall biosynthetic and repair genes[2][4]. The CWI pathway is a critical determinant of fungal pathogenicity, stress adaptation, and morphogenesis[1][3][5]. Its components are essential for the efficacy of antifungal drugs—such as echinocandins, which inhibit β-1,3-glucan synthesis—making it both a direct and indirect target for antifungal therapies[1][2][3][4]. However, "microbial cell wall/membrane integrity pathways" is not a molecular target but rather a pathway or class of targets. More precise molecular targets include specific sensors (Wsc1, Mid2), the GTPase (Rho1), protein kinase C (Pkc1), and MAP kinases (e.g., Slt2/Mpk1)[2][4][5]. Caveat: - The query target is not a single molecule, receptor, or enzyme but a broadly defined signaling pathway involving multiple proteins. Therefore, as written, it is not a canonical therapeutic target but a category encompassing numerous possible drug targets[1][2][4][5]. - To extract structured information for a database, individual molecular components within this pathway (e.g., "Rho1 GTPase", "Protein kinase C Pkc1", and "MAPK Slt2/Mpk1") should each receive their own canonical entry.

Other names

Cell wall integrity signaling pathwayCell wall integrity (CWI) pathwayFungal CWI pathwayMAPK cell wall integrity pathway

Inhibition of cell wall biosynthesis enzymes (e.g. β-1,3-glucan synthase inhibitors), Disruption of cell wall integrity signaling, Increased susceptibility to cell wall stress