MntC-Dependent Manganese Transport Is Essential for Staphylococcus aureus Oxidative Stress Resistance and Virulence

MSphere
Luke D HandkeAnnaliesa S Anderson

Abstract

Staphylococcus aureus is a human pathogen that has developed several approaches to evade the immune system, including a strategy to resist oxidative killing by phagocytes. This resistance is mediated by production of superoxide dismutase (SOD) enzymes which use manganese as a cofactor. S. aureus encodes two manganese ion transporters, MntABC and MntH, and a possible Nramp family manganese transporter, exemplified by S. aureus N315 SA1432. Their relative contributions to manganese transport have not been well defined in clinically relevant isolates. For this purpose, insertional inactivation mutations were introduced into mntC, mntH, and SA1432 individually and in combination. mntC was necessary for full resistance to methyl viologen, a compound that generates intracellular free radicals. In contrast, strains with an intact mntH gene had a minimal increase in resistance that was revealed only in mntC strains, and no change was observed upon mutation of SA1432 in strains lacking both mntC and mntH Similarly, MntC alone was required for high cellular SOD activity. In addition, mntC strains were attenuated in a murine sepsis model. To further link these observations to manganese transport, an S. aureus MntC protein lacking manganes...Continue Reading

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Oct 14, 2020·Archives of Microbiology·Vijay Hemmadi, Malabika Biswas
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Apr 4, 2020·Microbial Pathogenesis·Shalee K CarlsonEric Wilson
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May 31, 2019·Inorganic Chemistry·Rose C HadleyElizabeth M Nolan
Aug 10, 2021·Journal of Bacteriology·Eric D PengMichael P Schmitt

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Methods Mentioned

BETA
circular dichroism
isothermal titration calorimetry
phage display
surface plasmon resonance
PCR
PCRs
protein assay

Clinical Trials Mentioned

NCT02388165

Software Mentioned

AlignX
GraphPad
TMHMM
Origin
GraphPad Prism

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