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Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage

Schürmann, Nura and Forrer, Pascal and Casse, Olivier and Li, Jiagui and Felmy, Boas and Burgener, Anne-Valérie and Ehrenfeuchter, Nikolaus and Hardt, Wolf-Dietrich and Recher, Mike and Hess, Christoph and Tschan-Plessl, Astrid and Khanna, Nina and Bumann, Dirk. (2017) Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage. Nature Microbiology, 2. p. 16268.

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Official URL: http://edoc.unibas.ch/54573/

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Abstract

Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Imaging Core Facility (Biehlmaier)
UniBasel Contributors:Bumann, Dirk and Li, Jiagui and Ehrenfeuchter, Nikolaus and Schürmann, Nura and Casse, Olivier and Biehlmaier, Oliver and Recher, Mike and Khanna, Nina
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2058-5276
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:23 Nov 2018 10:53
Deposited On:19 Oct 2017 10:29

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