Manganese Detoxification by MntE Is Critical for Resistance to Oxidative Stress and Virulence of Staphylococcus aureus.

MBio
Caroline M GrunenwaldEric P Skaar

Abstract

Manganese (Mn) is an essential micronutrient critical for the pathogenesis of Staphylococcus aureus, a significant cause of human morbidity and mortality. Paradoxically, excess Mn is toxic; therefore, maintenance of intracellular Mn homeostasis is required for survival. Here we describe a Mn exporter in S. aureus, MntE, which is a member of the cation diffusion facilitator (CDF) protein family and conserved among Gram-positive pathogens. Upregulation of mntE transcription in response to excess Mn is dependent on the presence of MntR, a transcriptional repressor of the mntABC Mn uptake system. Inactivation of mntE or mntR leads to reduced growth in media supplemented with Mn, demonstrating MntE is required for detoxification of excess Mn. Inactivation of mntE results in elevated levels of intracellular Mn, but reduced intracellular iron (Fe) levels, supporting the hypothesis that MntE functions as a Mn efflux pump and Mn efflux influences Fe homeostasis. Strains inactivated for mntE are more sensitive to the oxidants NaOCl and paraquat, indicating Mn homeostasis is critical for resisting oxidative stress. Furthermore, mntE and mntR are required for full virulence of S. aureus during infection, suggesting S. aureus experiences Mn...Continue Reading

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Nov 7, 2019·Journal of Bacteriology·Srinand ParuthiyilJohn D Helmann
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Methods Mentioned

BETA
PCR
PCRs

Software Mentioned

Phyre2
CLC Genomics workbench
SEED Viewer
FigTree
PSPIRED
Agilent Mass Hunter Workstation
BioTek Gen5
GraphPad Prism
MEGA7
MEMSTAT

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