Short Communication

Archives of Microbiology

, Volume 181, Issue 5, pp 378-383

First online:

Deletion of the Aspergillus fumigatus lysine biosynthesis gene lysF encoding homoaconitase leads to attenuated virulence in a low-dose mouse infection model of invasive aspergillosis

  • Burghard LiebmannAffiliated withInstitut für Mikrobiologie, Universität Hannover
  • , Thomas W. MühleisenAffiliated withInstitut für Mikrobiologie, Universität Hannover
  • , Meike MüllerAffiliated withFraunhofer Institut für Toxikologie und Experimentelle Medizin
  • , Matthias HechtAffiliated withFraunhofer Institut für Toxikologie und Experimentelle Medizin
  • , Gerhard WeidnerAffiliated withInstitut für Mikrobiologie, Universität Hannover
  • , Armin BraunAffiliated withFraunhofer Institut für Toxikologie und Experimentelle Medizin
  • , Matthias BrockAffiliated withInstitut für Mikrobiologie, Universität Hannover
  • , Axel A. BrakhageAffiliated withInstitut für Mikrobiologie, Universität Hannover Email author 

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Abstract

Aspergillus fumigatus is an important pathogen of the immunocompromised host, causing pneumonia and invasive disseminated disease with high mortality. In order to determine the importance of lysine biosynthesis for growth and pathogenicity, the A. fumigatus lysF gene, encoding a homologue of the A. nidulans homoaconitase LysF, was cloned and characterized. Cosmid cosGTM encoding lysF complemented a lysF mutant of Aspergillus nidulans. A. fumigatus lysF was deleted, resulting in a lysine-auxotroph. This phenotype was complemented to the wild-type by supplementation of the medium with both L-lysine and α-aminoadipic acid, or transformation using cosmid cosGTM. To study the virulence of the lysF deletion mutant of A. fumigatus, a low-dose intranasal mouse infection model of invasive aspergillosis was optimized for immunosuppressed BALB/c mice, allowing the application of an infection dose as low as 5×103 conidia per mouse. In this murine model, the ΔlysF mutant was avirulent, suggesting that lysine biosynthesis, or at least a functional homoaconitase, is important for survival of A. fumigatus in vivo and a potential target for antifungal drugs.

Keywords

Aspergillus fumigatus Lysine biosynthesis Homoaconitase Animal model Invasive aspergillosis Antifungal drug target