Cited by 123Antifungal resistance and susceptibilityFungal and yeast genetics researchBiochemical and Molecular Research

Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus

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D'Enfert, C, Diaquin, M, Delit, A, Wuscher, N, Debeaupuis, J P, Huerre, M, Latge, J P·1996·Infection and Immunity

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.

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Crossref · 10.1128/iai.64.10.4401-4405.1996

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Authors
D'Enfert, C., Diaquin, M., Delit, A., Wuscher, N., Debeaupuis, J. P., Huerre, M., & Latge, J. P.
Affiliations
  • Laboratoire des Aspergillus and Unité d'Histopathologie, Institut Pasteur, Paris, France. denfert@pasteur.fr
  • Institut Pasteur (FR)
Corresponding author
  • Diaquin, M
  • Delit, A
  • Wuscher, N
  • Debeaupuis, J P
  • Huerre, M
Venue
Infection and Immunity
Published
1996-10
Volume
64
Issue
10
Pages
4401-4405
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
OpenAlex
W2129495031
Cited by
123
References
25
Citations by year
2025: 3 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 6 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 10 · 2012: 6
FWCI
0.33
Type
journal article
Language
en
Open access
Locations
  • Infection and Immunity (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
Aspergillus fumigatus, pyrG, orotidine 5'-monophosphate decarboxylase, conidial germination, invasive aspergillosis, virulence attenuation, alveolar macrophages, uridine supplementation, DNA-mediated gene transfer
MeSH terms
Animals, Aspergillus fumigatus, Female, Uracil, Uridine, Uridine Monophosphate, Virulence, Mice

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