Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense.

Autor:	Wiemann P; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA., Perevitsky A; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel., Lim FY; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA., Shadkchan Y; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel., Knox BP; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA., Landero Figueora JA; University of Cincinnati/Agilent Technologies Metallomics Center of the Americas, Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, USA., Choera T; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA., Niu M; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA., Steinberger AJ; Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA., Wüthrich M; Department of Pediatrics, University of Wisconsin, Madison, WI 53706, USA., Idol RA; Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA., Klein BS; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA; Department of Pediatrics, University of Wisconsin, Madison, WI 53706, USA; Department of Medicine, University of Wisconsin, Madison, WI 53706, USA., Dinauer MC; Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA., Huttenlocher A; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA; Department of Pediatrics, University of Wisconsin, Madison, WI 53706, USA., Osherov N; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: nosherov@post.tau.ac.il., Keller NP; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA; Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA. Electronic address: npkeller@wisc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 May 02; Vol. 19 (5), pp. 1008-1021.
DOI:	10.1016/j.celrep.2017.04.019
Abstrakt:	The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI) mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs), and reduced virulence in a non-neutropenic murine model. ΔaceA survival is remediated by dampening of host ROI (chemically or genetically) or enhancement of copper-exporting activity (CrpA) in A. fumigatus. Our study exposes a complex host/microbe multifactorial interplay that highlights the importance of host immune status and reveals key targetable A. fumigatus counter-defenses. (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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