Impact of glucose metabolism during pathogenesis of Aspergillus fumigatus

Ref ID: 18373

Author:

Christian B. Fleck , Ilse D. Jacobsen , Silvia Slesiona and Matthias
Brock

Author address:

Microbial Biochemistry and Physiology; Microbial Pathogenicity Mechanisms Leibniz Institute for Natural Product Research and Infection
1 1 2
Biology, -Hans Knoell Institute-, Beutenbergstr. 11a, 07745 Jena, Germany Contact: Matthias.brock@hki-jena

Full conference title:

Asperfest 8

Abstract:

Aspergillus fumigatus is the major cause of life-threatening invasive bronchopulmonary aspergillosis. Manifestation and progression of infection in the
immunocompromised host requires the efficient uptake and metabolism of nutrients. However, nutrient sources available and used by the pathogen are
mainly unknown. Here, we focused on the impact of glucose metabolism during pathogenesis. Glucose is highly abundant in the bloodstream and may
also be available within tissues. In order to activate glucose to glucose-6-phosphate A. fumigatus possesses two catalytically active hexose kinases,
glucokinase and hexokinase (Fleck and Brock, 2010). Analysis of deletion mutants and biochemical characterisations of the enzymes showed that
glucokinase possesses a low Km value for the substrate glucose and is required for rapid germination of conidia. In contrast, hexokinase possesses a broader
specificity for various sugars and is the dominating hexose kinase during vegetative growth. Deletion of either one enzyme caused only weak effects on
glucose, but the hexokinase was essential for growth on fructose. A mutant deleted in both genes revealed normal growth on most gluconeogenic nutrient
sources, but growth was abolished when glucose or fructose served assole carbon source. When tested in a murine model for invasive aspergillosis, both
single mutants caused disease comparable to the wild type. However, the double deletion mutant was strongly attenuated in virulence regardless the
immunosuppression regimen. Thus, glucose seems to provide an abundant nutrientsource during infection and interruption of glucose metabolism might
provide a tool to inhibit growth during pathogenesis. Fleck CB, Brock M. (2010) Aspergillus fumigatus catalytic gluco- and hexokinase: Expression
analysis, importance for germination, growth and conidiation. Eukaryot Cell 9:1120-35

Abstract Number: 51)

Conference Year: 2011

Link to conference website: NULL

New link: NULL

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