Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus.

Infection and immunity ·Vol. 64 ·No. 10 ·1996-10-00 ·Pages 4401-5

D'Enfert C, Diaquin M, Delit A, Wuscher N, Debeaupuis JP, Huerre M, Latge JP

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.

MeSH Terms

Animals Aspergillus fumigatus/metabolism,pathogenicity Female Mice Uracil/metabolism Uridine/metabolism Uridine Monophosphate/biosynthesis Virulence

Chemicals

Uracil Uridine Monophosphate Uridine

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

D'Enfert C

Laboratoire des Aspergillus and Unité d'Histopathologie, Institut Pasteur, Paris, France. denfert@pasteur.fr

Diaquin M

Delit A

Wuscher N

Debeaupuis J P

Huerre M

Latge J P

References (24)

24 references, click to expand

The induction and repression of nitrate reductase in the fungus Aspergillus nidulans.
Biochim Biophys Acta. 1966 Jan 11;113(1):51-6 PMID: 5940632
A stain for fungi in tissue sections and smears using Gomori's methenamine-silver nitrate technic.
Am J Clin Pathol. 1955 Aug;25(8):975-9 PMID: 14398663
[Experimental aspergillosis in the guinea pig. Dynamic study of the role of alveolar macrophages in the defense of the respiratory tract, after massive inhalation of Aspergillus fumigatus spores].
Rev Tuberc Pneumol (Paris). 1967 Sep-Oct;31(6):705-25 PMID: 4914810
The pathogenesis of experimental pulmonary aspergillosis. An ultrastructural study of alveolar macrophages after phagocytosis of a flavus spores in vivo.
Am J Pathol. 1971 Jan;62(1):57-74 PMID: 5538719
Pyrimidine biosynthesis in Aspergillus nidulans. Isolation and characterisation of mutants resistant to fluoropyrimidines.
Mol Gen Genet. 1975 Sep 29;140(2):165-73 PMID: 127929
Conditional virulence of a p-aminobenzoic acid-requiring mutant of Aspergillus fumigatus.
Infect Immun. 1976 Feb;13(2):527-32 PMID: 770331
Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes.
J Clin Invest. 1982 Mar;69(3):617-31 PMID: 7037853
Midazolam and fentanyl-fluanisone: assessment of anaesthetic effects in laboratory rodents and rabbits.
Lab Anim. 1984 Apr;18(2):143-6 PMID: 6748593
Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon.
J Clin Invest. 1985 Nov;76(5):1755-64 PMID: 3932471
Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.
Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189-93 PMID: 3523484
Isolation and characterization of auxotrophic mutants of Legionella pneumophila that fail to multiply in human monocytes.
Infect Immun. 1988 Jun;56(6):1449-55 PMID: 3372016
Getting started with yeast.
Methods Enzymol. 1991;194:3-21 PMID: 2005794
Virulence-associated chromosomal loci of Shigella flexneri identified by random Tn5 insertion mutagenesis.
Mol Microbiol. 1991 Jan;5(1):187-95 PMID: 1849606
Pathogenicity of Candida albicans auxotrophic mutants in experimental infections.
Infect Immun. 1991 Sep;59(9):3297-300 PMID: 1879944
An Aspergillus fumigatus alkaline protease mutant constructed by gene disruption is deficient in extracellular elastase activity.
Mol Microbiol. 1992 Jun;6(12):1663-71 PMID: 1495393
Selection of bacterial virulence genes that are specifically induced in host tissues.
Science. 1993 Jan 29;259(5095):686-8 PMID: 8430319
Virulence of alkaline protease-deficient mutants of Aspergillus fumigatus.
FEMS Microbiol Lett. 1993 Jan 1;106(1):39-46 PMID: 8095038
The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis.
Infect Immun. 1993 May;61(5):1650-6 PMID: 8478053
Virulence studies of Aspergillus nidulans mutants requiring lysine or p-aminobenzoic acid in invasive pulmonary aspergillosis.
Infect Immun. 1994 Dec;62(12):5255-60 PMID: 7960102
Antibiotic-based selection for bacterial genes that are specifically induced during infection of a host.
Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):669-73 PMID: 7846034
Avirulence of Candida albicans auxotrophic mutants in a rat model of oropharyngeal candidiasis.
FEMS Microbiol Lett. 1995 Feb 15;126(2):177-80 PMID: 7705609
Cloning and disruption of the gene encoding an extracellular metalloprotease of Aspergillus fumigatus.
Mol Microbiol. 1994 Dec;14(5):917-28 PMID: 7715453
Selection of multiple disruption events in Aspergillus fumigatus using the orotidine-5'-decarboxylase gene, pyrG, as a unique transformation marker.
Curr Genet. 1996 Jun;30(1):76-82 PMID: 8662213
Studies on the pathogenesis of experimental pulmonary aspergillosis.
Am J Pathol. 1967 Nov;51(5):769-88 PMID: 6054848

Article Info

Journal

Infection and immunity

Abbr.

Infect Immun

ISSN

0019-9567

DOI

10.1128/iai.64.10.4401-4405.1996

denfert@pasteur.fr

Published

1996-10-00

Pages

4401-5

Language

English

Region

United States

NLM ID

0246127

PMCID

PMC174389

Subset

External Links

PubMed source DOI: 10.1128/iai.64.10.4401-4405.1996 PMC Full Text View journal details

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Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus.

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