Kupfahl, Claudio;
Heinekamp, Thorsten;
Geginat, Gernot;
Ruppert, Thomas;
Härtl, Albert;
Hof, Herbert;
Brakhage, Axel A.
Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low‐dose mouse infection model
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Medientyp:
E-Artikel
Titel:
Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low‐dose mouse infection model
Beteiligte:
Kupfahl, Claudio;
Heinekamp, Thorsten;
Geginat, Gernot;
Ruppert, Thomas;
Härtl, Albert;
Hof, Herbert;
Brakhage, Axel A.
Erschienen:
Wiley, 2006
Erschienen in:Molecular Microbiology
Sprache:
Englisch
DOI:
10.1111/j.1365-2958.2006.05373.x
ISSN:
0950-382X;
1365-2958
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Summary</jats:title><jats:p>Gliotoxin is a secondary metabolite produced by several fungi including the opportunistic human pathogen <jats:italic>Aspergillus fumigatus</jats:italic>. As gliotoxin exerts immunosuppressive effects <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>, a role as a virulence determinant in invasive aspergillosis has been discussed for a long time but evidence has not been provided until now. Here, by the use of different selection marker genes <jats:italic>A. fumigatus</jats:italic> knock‐out strains were generated that are deficient for the non‐ribosomal peptide synthetase GliP, the putative key enzyme of the gliotoxin biosynthesis. Deletion of the <jats:italic>gliP</jats:italic> gene resulted in loss of gliotoxin production, as analysed by high performance liquid chromatography and tandem mass spectrometry. No differences in morphology or growth kinetics between wild‐type and <jats:italic>gliP</jats:italic>‐deletion strains were observed. <jats:italic>In vitro</jats:italic>, the culture supernatant of the <jats:italic>gliP</jats:italic>‐deficient strains showed a reduced cytotoxic effect on both macrophage‐like cells and T cell lines. In a low‐dose murine infection model of invasive aspergillosis, gliotoxin was detected in the lung and absent when mice were infected with the <jats:italic>gliP</jats:italic> deletion strain. However, <jats:italic>gliP</jats:italic> deletion strains showed no difference in virulence compared with the corresponding wild‐type strains. Taken together, the non‐ribosomal peptide synthetase GliP is essential for gliotoxin production in <jats:italic>A. fumigatus</jats:italic>. Gliotoxin is not required for pathogenicity of the fungus in immunocompromised mice, despite the fact that a reduced cytotoxicity of the culture supernatant of <jats:italic>gliP</jats:italic> deletion strains was demonstrated.</jats:p>