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.
Show evidence (3 references)
"They are the first cell wall-active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer."
Review establishing echinocandins as cell-wall-active agents that target the fungal-specific enzyme glucan synthase, which catalyzes beta-1,3-glucan biosynthesis — the target this node defines. Evidence source is OTHER as this is a review article.
"as non-competitive inhibitors of β-1,3-glucan synthase complex they target the fungal cell wall."
States the molecular mechanism of action — echinocandins are non-competitive inhibitors of the beta-1,3-glucan synthase complex acting on the fungal cell wall. Evidence source is OTHER as this is a review.
"Echinocandins (caspofungin, micafungin, anidulafungin), targeting β-1,3-glucan synthesis of the cell wall"
Confirms the named echinocandin agents and identifies beta-1,3-glucan synthesis of the cell wall as their shared target. Evidence source is OTHER as this is a review article.
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.
Show evidence (1 reference)
"inhibiting the formation of 1,3-β-D-glucan which is an essential component of the fungal cell wall."
Establishes that 1,3-beta-D-glucan formed by glucan synthase is an essential structural component of the assembled fungal cell wall — the load-bearing scaffold this node represents. Evidence source is OTHER as this is a review article.
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.
Show evidence (2 references)
"The decrease in 1,3-β-D-glucan results in the osmotic lysis of the cell, resulting in fungicidal activity against candida."
Directly states the terminal mechanism of this node — echinocandin-driven loss of 1,3-beta-D-glucan causes osmotic lysis and fungicidal activity against Candida. Evidence source is OTHER as this is a review article.
"they show good fungicidal (Candida spp.) or fungistatic (Aspergillus spp.) activity against the most important human pathogenic fungi"
Supports the consequence node's contrast between fungicidal activity against Candida and fungistatic activity against Aspergillus that follows from cell-wall disruption. Evidence source is OTHER as this is a review.
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.
Show evidence (1 reference)
"the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp."
Directly supports the gating claim that echinocandins have negligible activity against Cryptococcus, so the class is intrinsically excluded for cryptococcal disease. Evidence source is OTHER as this is a review article.