This is an antifungal drug-mechanism module structured as a biological pathway, not a specific disease. Its nodes are successive biological steps of fungal cell-wall beta-1,3-glucan biosynthesis (membrane glucan synthesis -> cell-wall assembly and integrity), with the intervention-conditional integrity-failure outcome recorded as a separate node, plus separate acquired- and intrinsic-resistance nodes; the echinocandin drug class that acts on the synthase step is described in the node text rather than modelled as a separate node. Disorder entries reference individual nodes via conforms_to (e.g., "fungal_cell_wall_glucan_synthesis_inhibition#beta-1,3-Glucan Synthesis at the Plasma Membrane by Fks Glucan Synthase"), and their echinocandin treatments point at the inhibited node via target_mechanisms (analogous to how cell-wall-active antibiotic treatments link to "bacterial_cell_wall_synthesis_inhibition#Peptidoglycan Cross-Linking by Penicillin-Binding Proteins"). Key conformance / treatment target: "beta-1,3-Glucan Synthesis at the Plasma Membrane by Fks Glucan Synthase" (the fungal-specific beta-1,3-glucan synthase that every echinocandin inhibits). The two resistance nodes capture the gating knowledge that distinguishes "an echinocandin is used" from real drug selection — acquired FKS hotspot resistance, and intrinsic resistance in Cryptococcus, for which the glucan-synthase target is not a viable drug target. Cryptococcus disease entries should NOT declare conforms_to against the positive target node; the intrinsic-resistance node documents that negative case. Other organism-level exclusions belong in antifungal_intrinsic_resistance_gating. As a high-precision operational curation boundary, rather than a claim of biological necessity, target-node conformance requires explicit FKS-catalyzed beta-1,3-glucan synthesis with GO:0006075 and GO:0003843, plus an evidence-bearing disease echinocandin treatment edge whose treatment_effect is INHIBITS. Mere fungal beta-glucan presence, a beta-D-glucan diagnostic biomarker, or host Dectin-1 recognition is insufficient. The infectious agent remains on the disorder, and this fungus-wide molecular activity does not require a CL cell type. A target-only conformer is sufficient; downstream integrity failure or lysis should be conformed only when disease-specific intervention evidence supports that outcome. Within this shared module, the outgoing edges from the target record treatment-selection and intervention-conditional consequences in their descriptions because the schema has no conditional causal-edge type. See projects/ANTIFUNGAL.md for the broader drug-fungus strategy and the complementary ergosterol-synthesis, ergosterol-membrane, and antimetabolite antifungal modules.
beta-1,3-Glucan Synthesis at the Plasma Membrane by Fks Glucan Synthase
therapeutic vulnerability
The committed biosynthetic step of the fungal cell wall: at the plasma membrane the beta-1,3-glucan synthase complex polymerizes UDP-glucose into beta-1,3-glucan, the essential load-bearing polymer of the wall. The catalytic subunit is encoded principally by FKS1; FKS2 supplies an additional, clinically relevant catalytic subunit in species such as Candida glabrata. Its 1,3-beta-D-glucan synthase activity transfers glucose into the growing glucan chain. Echinocandins (caspofungin, micafungin, anidulafungin, rezafungin) are cyclic lipopeptides that act as non-competitive inhibitors of this fungal-specific enzyme, blocking incorporation of glucose into beta-1,3-glucan and starving the wall of its principal structural polymer. Because mammalian cells lack a cell wall and a homologous synthase, the enzyme is absent from the host, making it a highly selective antifungal drug target. This is the central, most widely exploited node of the module and the canonical conformance / treatment target for echinocandin therapy (caspofungin, micafungin, anidulafungin, and rezafungin in invasive candidiasis/candidemia, and as an alternative in invasive aspergillosis).
Used by disorders
Aspergillosis
as Aspergillus beta-1,3-Glucan Synthesis by Fks Glucan Synthase
Downstream
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Cell-Wall Assembly and Integrity
The beta-1,3-glucan polymerized at the membrane is assembled into the wall, where it cross-links chitin and mannoproteins to build the intact, load-bearing fungal cell wall.
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FKS-Mediated Echinocandin Resistance
Under echinocandin selection, FKS hotspot substitutions can reduce the drug sensitivity of this catalytic target and permit treatment escape; this is a therapy-conditional resistance branch rather than a constitutive consequence of normal glucan synthesis.
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Intrinsic Echinocandin Resistance in Cryptococcus
In Cryptococcus, the glucan-synthase pathway is intrinsically refractory to clinically useful echinocandin activity; this organism-conditional edge records a target-selection exclusion rather than a downstream disease mechanism.
Cell-Wall Assembly and Integrity
effector
Beta-1,3-glucan synthesized at the membrane is the principal load-bearing polymer of the fungal cell wall: it forms the structural scaffold into which chitin and mannoproteins are cross-linked to build the intact, rigid wall that contains the high internal osmotic (turgor) pressure of the cell. This node represents the normal biological consequence of the upstream synthesis step — an assembled, mechanically competent wall — and is the structure that echinocandin inhibition of glucan synthase undermines. A wall in which beta-1,3-glucan is abundant is intact and osmotically stable; depletion of the polymer removes the scaffold on which assembly depends.
Downstream
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Cell-Wall Integrity Failure and Osmotic Lysis
When echinocandin treatment blocks upstream glucan synthesis, depletion of the load-bearing polymer converts normal wall assembly into integrity failure and osmotic lysis. This edge is explicitly intervention-conditional.
Cell-Wall Integrity Failure and Osmotic Lysis
consequence
When echinocandins inhibit beta-1,3-glucan synthase, the wall is depleted of its load-bearing polymer and its mechanical integrity fails; the high internal osmotic (turgor) pressure is no longer contained and ruptures the cell, producing osmotic lysis and cell death. Because the lethal outcome depends on a wall that the host does not possess, this lytic effect is selectively toxic to the fungus — the basis of the class's favorable therapeutic index. This is an intervention-conditional consequence of engaging the glucan-synthase target. Because treatments are modeled on disorder entries and the module has no conditional causal-edge type, the incoming edge description records that intervention conditionality explicitly. Activity is fungicidal against Candida and fungistatic (growth-inhibitory at hyphal tips) against Aspergillus.
Intrinsic Echinocandin Resistance in Cryptococcus
intrinsic resistance
The module's mechanism presupposes a beta-1,3-glucan wall in which the glucan-synthase target is essential and accessible. Some clinically important fungi fall outside that scope: Cryptococcus species display negligible echinocandin activity because inhibition of the target does not translate into useful antifungal activity. For cryptococcal disease, organism identity therefore excludes the echinocandin class. Cryptococcus-caused disease entries should NOT declare conforms_to against the positive glucan-synthase target node; this node documents the negative case. Other organism-level exclusions, including Mucorales, belong in the dedicated antifungal_intrinsic_resistance_gating module and are not asserted here without class-specific evidence.