Aspergillus fumigatus counteracts nitric oxide stress

Ref ID: 18494

Author:

Katrin Lapp,
Martin Vödisch,
Olaf Kniemeyer,
Ilse D. Jacobsen,
Thorsten Heinekamp,
Axel A. Brakhage

Author address:

Department of Molecular and Applied Microbiology  
Department of Microbial Pathogenicity Mechanisms,
Leibniz Institut of Natural Product Research and Infection Biology - Hans-Knöll-Institut

Full conference title:

11 th European Conference on Fungal Genetics

Abstract:

Aspergillus fumigatus is a saprophytic living mold that can cause life8208;threatening infections in
immunocompromised patients. To improve diagnosis and therapy a detailed knowledge of the processes related
to host8208;pathogen interaction is required. In the lung, inhaled conidia are confronted with immune effector cells.
After recognition of the conidia are phagocytosed and attacked by host8208;derived reactive oxygen species (ROS) and
antimicrobial proteins. In recent studies it was found that macrophages and neutrophil granulocytes can also form
nitric oxide intermediates (RNI) that are putatively involved in killing of the fungus. Because both radicals are
present in infected tissue it is very likely that they interact to form highly reactive intermediates like peroxynitrite.
A. fumigatus produces several enzymes potentially involved in RNI detoxification. Two flavohemoglobins, FhpA
and FhpB, convert NO to nitrate, and the S8208;nitrosoglutathion (GSNO) reductase, GnoA, reduces GSNO to
ammonium and glutathion disulphide (GSSG). To elucidate the role of these enzymes in detoxification of RNI single
and double deletion mutants of FhpA, FhpB and GnoA encoding genes were generated. Mutant strains revealed
enhanced sensitivity against the NO donor DETA8208;NO. Furthermore,  8710;gnoA mutants were negatively affected in
germination. To investigate the role of RNI and its detoxification in fungal pathogenicity virulence of the DgnoA
mutant was analysed in a cortisone acetate murine infection model for invasive aspergillosis. However, no
difference in pathogenicity was detectable compared to the wild type and complemented strains. Therefore, the
ability to detoxify host8208;derived RNI does not have a major influence on virulence of the human pathogenic fungus
A. fumigatus.

Abstract Number: PR6.5

Conference Year: 2012

Link to conference website: http://www.ecfg.info/images/Abstract_Book_Electronic.pdf

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