Journal article
Disruption of Phosphate Homeostasis Sensitizes Staphylococcus aureus to Nutritional Immunity
Infection and immunity, Vol.88(6), e00102
05/20/2020
DOI: 10.1128/IAI.00102-20
PMCID: PMC7240092
PMID: 32205403
Abstract
To control infection, mammals actively withhold essential nutrients, including the transition metal manganese, by a process termed nutritional immunity. A critical component of this host response is the manganese-chelating protein calprotectin. While many bacterial mechanisms for overcoming nutritional immunity have been identified, the intersection between metal starvation and other essential inorganic nutrients has not been investigated. Here, we report that overexpression of an operon encoding a highly conserved inorganic phosphate importer, PstSCAB, increases the sensitivity of
to calprotectin-mediated manganese sequestration. Further analysis revealed that overexpression of
does not disrupt manganese acquisition or result in overaccumulation of phosphate by
However, it does reduce the ability of
to grow in phosphate-replete defined medium. Overexpression of
does not aberrantly activate the phosphate-responsive two-component system PhoPR, nor was this two-component system required for sensitivity to manganese starvation. In a mouse model of systemic staphylococcal disease, a
-overexpressing strain is significantly attenuated compared to wild-type
This defect is partially reversed in a calprotectin-deficient mouse, in which manganese is more readily available. Given that expression of
is regulated by PhoPR, these findings suggest that overactivation of PhoPR would diminish the ability of
to resist nutritional immunity and cause infection. As PhoPR is also necessary for bacterial virulence, these findings imply that phosphate homeostasis represents a critical regulatory node whose activity must be precisely controlled in order for
and other pathogens to cause infection.
Details
- Title: Subtitle
- Disruption of Phosphate Homeostasis Sensitizes Staphylococcus aureus to Nutritional Immunity
- Creators
- Jessica L Kelliher - University of Illinois Urbana-ChampaignErin B Brazel - University of AdelaideJana N Radin - University of Illinois Urbana-ChampaignEliot S Joya - University of Illinois Urbana-ChampaignPaola K Párraga Solórzano - ArmadaStephanie L Neville - Peter Doherty InstituteChristopher A McDevitt - Peter Doherty InstituteThomas E Kehl-Fie - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.88(6), e00102
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/IAI.00102-20
- PMID
- 32205403
- PMCID
- PMC7240092
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Grant note
- R21 AI149115 / NIAID NIH HHS R01 AI118880 / NIAID NIH HHS K22 AI104805 / NIAID NIH HHS
- Language
- English
- Date published
- 05/20/2020
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618509902771
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