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Ophthalmology, University of Oklahoma"],"award-info":[{"award-number":["Unrestricted Grant to Dept. Ophthalmology, University of Oklahoma"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Unrestricted Grant to Dept. Ophtalmology, University of Pittsburgh"],"award-info":[{"award-number":["Unrestricted Grant to Dept. Ophtalmology, University of Pittsburgh"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>\n                    Elucidate the influence of glucose metabolic pathways on\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    lung and corneal infection.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>A. fumigatus acuF<\/jats:italic>\n                    and\n                    <jats:italic>creA<\/jats:italic>\n                    genes were deleted in an\n                    <jats:italic>mcherry<\/jats:italic>\n                    -expressing strain. The mutants were tested for alterations in radial growth, cell wall composition by fluorescence staining assays, and antifungal sensitivity through broth microdilution assays. Hyphal penetration of the strains through explanted porcine corneas was tracked by confocal microscopy using the mCherry signal. Virulence was evaluated in established models of invasive pulmonary aspergillosis (IPA) and fungal keratitis (FK) using C57BL\/6J mice.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Deletion of the\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    phosphoenolpyruvate carboxykinase (\n                    <jats:italic>acuF<\/jats:italic>\n                    ) resulted in a dependency on exogenous glucose to support growth\n                    <jats:italic>in vitro<\/jats:italic>\n                    , but did not impact virulence in either the IPA or FK models. Loss of the carbon catabolite repressor CreA resulted in a broad dysregulation of carbon metabolic pathways and altered cell wall homeostasis. Surprisingly, whereas the\n                    <jats:italic>\u0394creA<\/jats:italic>\n                    remained fully virulent in the lung, the mutant was unable to establish infection in the FK model. This\n                    <jats:italic>in vivo<\/jats:italic>\n                    phenotype corresponded to an inability of\n                    <jats:italic>\u0394creA<\/jats:italic>\n                    to physically invade porcine corneal explants, which we attributed to a marked reduction in cell wall chitin content.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Gluconeogenesis is dispensable for\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    lung and corneal infection, suggesting tissue-derived glucose supports fungal growth in both environments. Loss of CreA disrupts glucose assimilation, its synthesis into chitin and, consequently, cell rigidity and hyphal invasion into the dense corneal stroma. Thus, CreA and other cell wall regulatory proteins may serve as targets for novel FK antifungals.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.13.744696","type":"posted-content","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:50:19Z","timestamp":1786683019000},"source":"Crossref","is-referenced-by-count":0,"title":["A cornea-specific role for the\n                  <i>Aspergillus fumigatus<\/i>\n                  carbon catabolite repressor, CreA, in tissue penetration and infection establishment"],"prefix":"10.64898","author":[{"given":"Becca L.","family":"Wells","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi Ying","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Sciences, Manchester Metropolitan 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