Decoding the Dynamic Interface: Intracellular Signaling and Fungal Cell Wall Remodeling in Immune Evasion

Fungal pathogenesis represents a rapidly evolving field, underscored by a staggering four-fold increase in the emergence of fungal infections over the last four decades, positioning these pathogens as escalating threats to both human health and global agriculture. The fungal cell wall, traditionally viewed as a passive structural barrier, is now recognized as a highly dynamic interface critically involved in mediating pathogen-host interactions. Recent investigations have emphasized the importance of cell wall polysaccharides, particularly β(1,3)-glucan, in immune recognition and evasion, where regulated exposure or masking can dramatically alter host responses.Key investigations have identified critical regulatory hubs, such as the calcineurin pathway and the Mkc1p (MAPK) kinase cascade, as central orchestrators of chitin deposition and β(1,3)-glucan unmasking. Calcineurin, a Ca2+-calmodulin-dependent phosphatase, is essential for maintaining cell wall integrity under stress by regulating chitin synthase activity, while the Cell Wall Integrity (CWI) pathway, terminating in Mkc1p, responds to physical breaches by reinforcing the polysaccharide matrix. Beyond traditional signaling hubs, the metabolic pathways fueling cell wall biosynthesis are emerging as high-value therapeutic vulnerabilities. Specifically, the development of fungicides targeting UDP-glucose 4-epimerase (UGE), a key enzyme in the Leloir pathway represents a promising strategy to disrupt cell wall integrity by impairing the synthesis of critical precursors like UDP-galactose. However, despite these insights, the precise intracellular signaling cascades and molecular mechanisms governing these remodeling events remain incompletely understood. As debates continue regarding the sequence, crosstalk, and functional consequences of intracellular signals, uncovering these pathways will deepen our understanding of pathogen survival and adaptation.This Research Topic aims to delineate the intracellular signaling mechanisms orchestrating fungal cell wall remodeling and their impact on immune evasion. Specifically, it seeks to dissect how signaling regulators, such as calcineurin and Mkc1p kinase, govern chitin deposition and glucan masking or exposure. The objectives include identifying novel molecular players, mapping pathway cross-talk, and elucidating cell wall composition changes during infection. Through the integration of advanced molecular biology methods, genetic manipulation, and systems biology approaches, the goal is to uncover targets for innovative antifungal therapies that disrupt immune evasion and bolster host defense.The scope of this Research Topic encompasses in-depth exploration of intracellular signaling events driving cell wall dynamics in fungal pathogens, with a primary focus on mechanisms relevant to immune evasion. Studies centered on pathogenic fungi affecting humans, animals, or plants are within range; however, work limited to non-pathogenic models or unrelated cell wall chemistries falls outside the scope.To gather further insights in these boundaries, we welcome articles addressing, but not limited to, the following themes:- Functional analysis of calcineurin and Mkc1p kinase signaling pathways.- Molecular mechanisms underlying β(1,3)-glucan exposure and masking.- Crosstalk between chitin synthesis and signaling regulators during pathogenesis.- Manipulation of cell wall remodeling using genetic and chemical tools.- Host immune responses triggered by dynamic changes in cell wall composition.Elucidate action mechanism of fungal UGE targeting antifungal compounds.- Identification of novel molecular targets for antifungal therapy.- Comparative studies of cell wall-associated immune modulation across fungal species.We welcome original research, reviews, and perspective articles focusing on fungal pathogens of humans, animals, or plants. Studies involving non-pathogenic models must clearly demonstrate the translational relevance to pathogenic species. Topic editors: Tofazzal Islam, Domingo Martinez-Soto Source: https://www.frontiersin.org/research-topics/82795/decoding-the-dynamic-interface-intracellular-signaling-and-fungal-cell-wall-remodeling-in-immune-evasion