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Cell Host Microbe. 2016 Jun 8;19(6):814-25. doi: 10.1016/j.chom.2016.05.005.

Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration.

Author information

1
Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697-4025, USA; Institute for Immunology, University of California, Irvine, Irvine, CA 92697-4120, USA.
2
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697-3900, USA.
3
Department of Biochemistry and Chemistry, Vanderbilt University, Nashville, TN 37232-8725, USA.
4
Department of Pathology and Laboratory Medicine, University of Southern California, Los Angeles, CA 90089-9092, USA.
5
Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA 92697-4800, USA.
6
Department of Biology, University of Rome, Tor Vergata, 00173 Roma, Italy.
7
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697-3900, USA; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697-3958, USA.
8
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA; Tennessee Valley Healthcare System, US Department of Veterans Affairs, Nashville, TN 37212, USA.
9
Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697-4025, USA; Institute for Immunology, University of California, Irvine, Irvine, CA 92697-4120, USA. Electronic address: manuelar@uci.edu.

Abstract

Neutrophils hinder bacterial growth by a variety of antimicrobial mechanisms, including the production of reactive oxygen species and the secretion of proteins that sequester nutrients essential to microbes. A major player in this process is calprotectin, a host protein that exerts antimicrobial activity by chelating zinc and manganese. Here we show that the intestinal pathogen Salmonella enterica serovar Typhimurium uses specialized metal transporters to evade calprotectin sequestration of manganese, allowing the bacteria to outcompete commensals and thrive in the inflamed gut. The pathogen's ability to acquire manganese in turn promotes function of SodA and KatN, enzymes that use the metal as a cofactor to detoxify reactive oxygen species. This manganese-dependent SodA activity allows the bacteria to evade neutrophil killing mediated by calprotectin and reactive oxygen species. Thus, manganese acquisition enables S. Typhimurium to overcome host antimicrobial defenses and support its competitive growth in the intestine.

PMID:
27281571
PMCID:
PMC4901528
DOI:
10.1016/j.chom.2016.05.005
[Indexed for MEDLINE]
Free PMC Article

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