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Triazoles, the primary therapeutic options to combat invasive aspergillosis (IA), target the biosynthesis of ergosterol, a vital component of the fungal cell membrane. Unfortunately, resistance to this class of medical therapeutics has arisen globally and now threatens the future usefulness of these compounds for antifungal treatment. Infection with\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      with acquired triazole resistance increases an already high associated mortality rate and reduces the limited arsenal of therapeutic options to combat IA. How this specific fungal pathogen obtains resistance remains poorly understood. In this study, we show that loss of the previously uncharacterized\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      spindle assembly checkpoint (SAC) components, SldA or SldB, resulted in a heteroresistance phenotype to multiple mold active medical triazoles and to compounds inhibiting ergosterol biosynthesis at points upstream of the triazole target, Cyp51A. Consistent with conserved roles in mitotic fidelity, loss of either component resulted in the production of conidia characterized by an increased genome size, suggestive of potential aneuploidy development. Interestingly, we find that heteroresistance of the \u2206\n                      <jats:italic toggle=\"yes\">sldA<\/jats:italic>\n                      or \u2206\n                      <jats:italic toggle=\"yes\">sldB<\/jats:italic>\n                      conidial populations was only evident in response to ergosterol biosynthesis pathway inhibition and not seen with other external stress. Our findings support the hypothesis that specific links exist between SAC function and resistance to ergosterol biosynthesis perturbation in\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The rising threat of antifungal resistance in\n                        <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                        , a filamentous fungal species which remains one of the leading causes of human invasive infections, is an increasingly relevant concern to public health worldwide. The mode and mechanism of triazole resistance acquisition remain an understudied issue for this opportunistic pathogen. This work uncovers a novel role for a functional spindle assembly checkpoint in maintaining susceptibility to ergosterol biosynthesis inhibitors, including the triazole antifungal drug class.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00536-25","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T09:44:48Z","timestamp":1750067088000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Loss of the\n                    <i>Aspergillus fumigatus<\/i>\n                    spindle assembly checkpoint components, SldA or SldB, generates triazole heteroresistant conidial populations"],"prefix":"10.1128","volume":"13","author":[{"given":"Ashley 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