title: Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus.
abstract: Aspergillus fumigatus mutants that are deficient in the de novo UMP biosynthesis pathway because of a mutation in the pyrG gene encoding orotidine-5'-phosphate decarboxylase (and therefore auxotrophic for uridine or uracil) were evaluated in a murine model of invasive aspergillosis. These mutants were entirely nonpathogenic, and mutant conidia remained ungerminated in alveolar macrophages. Both the germination and virulence defects could be restored by supplementing the drinking water of the animals with uridine. DNA-mediated transformation of one of the pyrG mutants with the Aspergillus niger pyrG gene also restored virulence. These results suggest that uridine and uracil are limiting in the lung environment, thus preventing conidium germination and hence virulence of the pyrG mutants.
authors.affiliation: Laboratoire des Aspergillus and Unité d'Histopathologie, Institut Pasteur, Paris, France. denfert@pasteur.fr
authors.forename: C
authors.initials: C
authors.lastname: D'Enfert
authors.forename: M
authors.initials: M
authors.lastname: Diaquin
authors.forename: A
authors.initials: A
authors.lastname: Delit
authors.forename: N
authors.initials: N
authors.lastname: Wuscher
authors.forename: J P
authors.initials: JP
authors.lastname: Debeaupuis
authors.forename: M
authors.initials: M
authors.lastname: Huerre
authors.forename: J P
authors.initials: JP
authors.lastname: Latge
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D051379:Mice; D014498:Uracil / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism*; D014542:Uridine Monophosphate / Q000096:biosynthesis; D014774:Virulence
chemical_list: D014498:Uracil; D014542:Uridine Monophosphate; D014529:Uridine