Pathogenesis and Triazole Resistance in Aspergillus fumigatus: A Narrative Review Across the Host Immune Spectrum and One Health Context.

This narrative review explores triazole resistance and pathogenesis of Aspergillus fumigatus (A. fumigatus) under a unified One Health framework, integrating evidence across host immune spectrums, agricultural environmental selection pressures, veterinary aspergillosis and clinical antifungal management. We illustrate layered host-fungus immune interactions underlying distinct clinical aspergillosis phenotypes, and delineate core resistance mechanisms including cyp51-related target alterations, enhanced efflux pump activity, biofilm-mediated tolerance and adaptive stress response rewiring. Special emphasis is placed on cross-sector transmission pathways of azole-resistant A. fumigatus (ARAF) originating from agricultural ecosystems, as well as surveillance deficits and public health risks linked to animal intermediate hosts. Novel antifungal agents, such as olorofim, fosmanogepix, rezafungin, ibrexafungerp, and T-2307, along with targeted delivery and immunomodulatory adjunct therapies for resistant aspergillosis, are also summarized. Literature published 2020-2026 was retrieved from PubMed via Boolean search strategies, with supplementary manual screening of landmark reference lists to include pivotal earlier studies. Only peer-reviewed original studies, epidemiological surveillance reports, and review articles with complete clinical or experimental datasets were incorporated following rigorous screening. Most studies discuss clinical or agricultural resistance separately, lacking integrated analyses covering human, animal, and environmental dimensions. Major knowledge gaps persist regarding horizontal gene transfer of resistance mutations, cross-species transmission chains, and translational applications of environmental monitoring data. This review summarizes existing research bottlenecks and proposes integrated multi-sector prevention and control strategies from a One Health perspective to curb the growing threat of triazole-resistant aspergillosis.