Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant.

Autor:	Amich J; Department of Medicine II and Center for Interdisciplinary Clinical Research, University Hospital Würzburg, Würzburg, Germany Amich_J@ukw.de sven.krappmann@uk-erlangen.de.; Research Center for Infectious Diseases, Julius Maximilians University, Würzburg, Germany., Dümig M; Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., O'Keeffe G; Department of Biology, Maynooth University, Co. Kildare, Ireland., Binder J; Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Doyle S; Department of Biology, Maynooth University, Co. Kildare, Ireland., Beilhack A; Department of Medicine II and Center for Interdisciplinary Clinical Research, University Hospital Würzburg, Würzburg, Germany., Krappmann S; Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Amich_J@ukw.de sven.krappmann@uk-erlangen.de.; Medical Immunology Campus Erlangen, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2016 Mar 24; Vol. 84 (4), pp. 917-929. Date of Electronic Publication: 2016 Mar 24 (Print Publication: 2016).
DOI:	10.1128/IAI.01124-15
Abstrakt:	Fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. To date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. This is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent. Here, we have investigated sulfur (S) utilization by the human-pathogenic mold Aspergillus fumigatus during invasive growth. Our data reveal that inorganic S compounds or taurine is unlikely to serve as an S source during invasive pulmonary aspergillosis since a sulfate transporter mutant strain and a sulfite reductase mutant strain are fully virulent. In contrast, the S-containing amino acid cysteine is limiting for fungal growth, as proven by the reduced virulence of a cysteine auxotroph. Moreover, phenotypic characterization of this strain further revealed the robustness of the subordinate glutathione redox system. Interestingly, we demonstrate that methionine synthase is essential for A. fumigatus virulence, defining the biosynthetic route of this proteinogenic amino acid as a potential antifungal target. In conclusion, we provide novel insights into the nutritional requirements ofA. fumigatus during pathogenesis, a prerequisite to understanding and fighting infection. (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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