Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus
Open accessAbstract
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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- 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
- Publisher
- American Society for Microbiology
- Published
- 1996-10
- Volume
- 64
- Issue
- 10
- Pages
- 4401-4405
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC174389
- 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
- green
- europepmc.org
- 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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