This is an antifungal drug-mechanism (species-level gating) module, not a specific disease. It is the antifungal analog of the antibacterial intracellular_pathogen_persistence module: the nodes are gating principles, not enzyme targets. Disorder entries for mycoses reference nodes via conforms_to (e.g., "antifungal_intrinsic_resistance_gating#Species-Level Intrinsic Antifungal Resistance"), and their treatments may point at the gating node via target_mechanisms to record why a whole class is or is not an option. Key conformance / gating target: "Species-Level Intrinsic Antifungal Resistance" (the Aspergillus/fluconazole, Cryptococcus/echinocandin, Mucorales/voriconazole+ echinocandin exclusions). A conforming disease typically ALSO conforms to a target-based antifungal module (ergosterol synthesis, ergosterol-membrane binding, glucan synthase, or nucleic-acid antimetabolite) for the molecular mechanism of whatever drug remains viable, with this module explaining which classes are excluded a priori by the infecting species. See projects/ANTIFUNGAL.md (the antifungal_intrinsic_resistance_gating row of the proposed-module table and the "Intrinsic species resistance" axis), where this module is positioned as the lineage-level treatment-exclusion gate. Conformance to the intrinsic-resistance node requires evidence for a fixed genus-, species-, or order-level exclusion of a named antifungal agent or mechanistic class; organism identity predicting absent or negligible activity of that agent or class before isolate-level susceptibility testing is sufficient. Acquired isolate resistance, target mutation, or biofilm-associated tolerance alone is not sufficient and belongs on the acquired-resistance node or a target-specific module. The intrinsic and acquired nodes are parallel gating arms: neither is asserted to cause the other, and a disorder may conform to either arm without duplicating the other one. NTR: no GO biological-process term precisely represents constitutive lineage-level antifungal insusceptibility; GO:0009410 denotes a response to a xenobiotic stimulus and is therefore not asserted as an exact binding here.
Species-Level Intrinsic Antifungal Resistance
intrinsic resistance
The lineage identity of the infecting fungus excludes a named antifungal agent or whole mechanistic class before any susceptibility result, because a required target is absent, divergent, or non-viable, or the agent otherwise has negligible lineage-wide activity. This is the central gating principle of the module and its canonical conformance / gating target. Three fixed, phylogeny-determined exclusions recur clinically: (1) Aspergillus species are intrinsically resistant to fluconazole, so invasive aspergillosis requires a mold-active azole (voriconazole, isavuconazole, posaconazole, itraconazole) or amphotericin B; (2) Cryptococcus species display negligible susceptibility to the echinocandins — the β-1,3-glucan-synthase target exists but is not a viable drug target — so cryptococcosis is treated with amphotericin B, flucytosine, and fluconazole, never an echinocandin; and (3) the Mucorales (agents of mucormycosis) are intrinsically resistant to both voriconazole and the echinocandins, leaving amphotericin B (typically lipid formulations) or isavuconazole as the only active options. Because these exclusions track monophyletic taxonomic groups, members of the same order behave alike, and empiric drug choice is therefore gated by organism identification rather than by in-vitro testing of the individual isolate.
Species-level intrinsic insusceptibility to the antifungal
Relation: this pathophysiological event involves this biological process
This pathophysiological event involves Species-level intrinsic insusceptibility to the antifungal.
Used by disorders
Otomycosis
as Aspergillus intrinsic fluconazole resistance
Downstream
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Resistance-Gated Narrowing of Antifungal Options
A fixed lineage-level exclusion removes an agent or class before isolate-level testing and therefore narrows empiric treatment options.
Acquired Multidrug Resistance in Emerging Species (Candida auris)
adaptive escape
Beyond the phylogenetically fixed intrinsic exclusions, a second gating layer arises from emerging pathogens that acquire resistance across several antifungal classes at once. The exemplar is Candida auris, an emerging multidrug-resistant species in which acquired resistance to the azoles, echinocandins, and polyenes can co-occur, collapsing the available armamentarium and forcing susceptibility-guided, often last-line therapy. More broadly, multidrug resistance to the azoles, echinocandins, and polyenes is increasingly reported across Candida species (notably C. glabrata and now C. auris), driven by overall antifungal use, subtherapeutic drug levels, and biofilm sequestration. This node captures why species identification must be coupled to surveillance of acquired resistance: an organism whose class is nominally available may nonetheless be untreatable with it, so empiric choice and stewardship must account for the emergence of pan-resistant strains.
Downstream
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Resistance-Gated Narrowing of Antifungal Options
Acquired resistance spanning several major antifungal classes removes otherwise nominal options and forces susceptibility-guided treatment.
Resistance-Gated Narrowing of Antifungal Options
consequence
The shared consequence of the two parallel resistance arms is a smaller set of viable antifungal choices. Fixed lineage-level exclusions constrain empiric therapy from organism identification, while acquired multidrug resistance can remove additional agents after susceptibility testing. Convergence on this node does not assert that intrinsic resistance causes acquired resistance or vice versa.