{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:04:38Z","timestamp":1782281078712,"version":"3.54.5"},"posted":{"date-parts":[[2025,12,4]]},"group-title":"Microbiology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                  poses a significant threat to human well-being, in part due to the increasing emergence of strains resistant to frontline antifungal therapy. In this study, we observe that the gene,\n                  <jats:italic>arvA<\/jats:italic>\n                  , is required for\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  morphogenesis, antifungal drug susceptibility, and cell wall homeostasis. Intriguingly, our study reveals novel morphological and growth aberrations in the absence of\n                  <jats:italic>arvA<\/jats:italic>\n                  . Loss of\n                  <jats:italic>arvA<\/jats:italic>\n                  results in hyper-swollen conidia that give rise to stunted, polarity-deficient hyphae in numerous environmental conditions, indicating a pivotal role for\n                  <jats:italic>arvA<\/jats:italic>\n                  in\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  morphogenesis. Surprisingly, despite these severe\n                  <jats:italic>in vitro<\/jats:italic>\n                  morphological and cell wall defects,\n                  <jats:italic>arvA<\/jats:italic>\n                  was not required for morbidity and mortality in immunologically distinct murine models of invasive pulmonary aspergillosis (IPA). However, growth in natural calf lung surfactant was able to normalize\n                  <jats:italic>\u0394arvA<\/jats:italic>\n                  growth with the wild-type strain suggesting lung surfactant may partially complement the severe\n                  <jats:italic>in vitro<\/jats:italic>\n                  morphological defects of\n                  <jats:italic>arvA<\/jats:italic>\n                  loss\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Taken together our observations reveal\n                  <jats:italic>arvA<\/jats:italic>\n                  as a mediator of\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  antifungal drug susceptibility and highlight the complex and ill-defined pulmonary nutrient environment\u2019s role in mediating\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  pathogenesis and disease progression.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    is a challenging fungal pathogen in the clinic in part due to increasing azole drug resistance. In this study, we observe that loss of the\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    gene\n                    <jats:italic>arvA<\/jats:italic>\n                    results in increased azole susceptibility and significant\n                    <jats:italic>in vitro<\/jats:italic>\n                    morphological changes highlighted by hyper-swollen conidia that yield stunted and polarity deficient hyphae.\n                  <\/jats:p>\n                  <jats:p>\n                    Importantly, despite these severe\n                    <jats:italic>in vitro<\/jats:italic>\n                    morphological and growth abnormalities,\n                    <jats:italic>\u0394arvA<\/jats:italic>\n                    surprisingly retains full pathogenicity and virulence in two immunologically distinct murine models of invasive pulmonary aspergillosis. These results challenge our understanding of the in-host environment and how it mediates fungal morphogenesis and pathogenesis. These results, consequently, not only enhances our understanding of the role of\n                    <jats:italic>arvA<\/jats:italic>\n                    in\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    morphogenesis and drug susceptibility, but further emphasizes the importance of\n                    <jats:italic>in vivo<\/jats:italic>\n                    animal models in fully evaluating potential antifungal drug targets.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.04.692327","type":"posted-content","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:31:50Z","timestamp":1765197110000},"source":"Crossref","is-referenced-by-count":0,"title":["Insights into Aspergillus fumigatus morphogenesis and pathogenesis through the putative lipid transporter 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