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 -> cell-wall integrity failure and osmotic lysis), with an acquired-resistance branch and an intrinsic-resistance gating branch; 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 Glucan Synthase (FKS1)"), 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 Glucan Synthase (FKS1)" (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 organisms (Cryptococcus, Mucorales) for which the glucan-synthase target is not a viable drug target. Conforming entries for those organisms should NOT declare conforms_to against the target node; the intrinsic-resistance node documents the negative/gating case. 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 Glucan Synthase (FKS1)
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 by FKS1 (and the paralog FKS2), and 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 the most cleanly 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).
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
Hotspot amino-acid substitutions in the FKS-encoded glucan-synthase subunits lower the enzyme's drug sensitivity, the basis of acquired resistance at this catalytic step.
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Intrinsic Resistance in Organisms Lacking an Echinocandin-Susceptible Wall
In Cryptococcus and the Mucorales the glucan-synthase target is not a viable drug target, so inhibition at this step has no useful effect regardless of dose.
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 beta-1,3-glucan is depleted, the wall loses the scaffold that maintains its mechanical integrity, so unopposed internal turgor ruptures the cell.
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 the terminal consequence of engaging the glucan-synthase target. Activity is fungicidal against Candida and fungistatic (growth-inhibitory at hyphal tips) against Aspergillus.
Intrinsic Resistance in Organisms Lacking an Echinocandin-Susceptible Wall
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 (the wall's reliance on the target and the drug-target interaction differ such that inhibition does not translate into killing), and the Mucorales are intrinsically resistant to echinocandins. For these organisms, organism identity alone excludes the echinocandin class a priori, regardless of dose or in vitro testing — the clearest example of mechanism gating drug choice on the antifungal side. Disorder entries for Cryptococcus- or Mucorales-caused disease should NOT declare conforms_to against the glucan-synthase target node; this node documents the negative case and the reason echinocandin therapy is excluded (cryptococcal disease is treated with amphotericin B, flucytosine, and azoles; mucormycosis with amphotericin B or isavuconazole).