Journal article
A Superoxide Dismutase Capable of Functioning with Iron or Manganese Promotes the Resistance of Staphylococcus aureus to Calprotectin and Nutritional Immunity
PLoS pathogens, Vol.13(1), pp.e1006125-e1006125
01/01/2017
DOI: 10.1371/journal.ppat.1006125
PMCID: PMC5245786
PMID: 28103306
Abstract
Staphylococcus aureus is a devastating mammalian pathogen for which the development of new therapeutic approaches is urgently needed due to the prevalence of antibiotic resistance. During infection pathogens must overcome the dual threats of host-imposed manganese starvation, termed nutritional immunity, and the oxidative burst of immune cells. These defenses function synergistically, as host-imposed manganese starvation reduces activity of the manganese-dependent enzyme superoxide dismutase (SOD). S. aureus expresses two SODs, denoted SodA and SodM. While all staphylococci possess SodA, SodM is unique to S. aureus, but the advantage that S. aureus gains by expressing two apparently manganese-dependent SODs is unknown. Surprisingly, loss of both SODs renders S. aureus more sensitive to host-imposed manganese starvation, suggesting a role for these proteins in overcoming nutritional immunity. In this study, we have elucidated the respective contributions of SodA and SodM to resisting oxidative stress and nutritional immunity. These analyses revealed that SodA is important for resisting oxidative stress and for disease development when manganese is abundant, while SodM is important under manganese-deplete conditions. In vitro analysis demonstrated that SodA is strictly manganese-dependent whereas SodM is in fact cambialistic, possessing equal enzymatic activity when loaded with manganese or iron. Cumulatively, these studies provide a mechanistic rationale for the acquisition of a second superoxide dismutase by S. aureus and demonstrate an important contribution of cambialistic SODs to bacterial pathogenesis. Furthermore, they also suggest a new mechanism for resisting manganese starvation, namely populating manganese-utilizing enzymes with iron.
Details
- Title: Subtitle
- A Superoxide Dismutase Capable of Functioning with Iron or Manganese Promotes the Resistance of Staphylococcus aureus to Calprotectin and Nutritional Immunity
- Creators
- Yuritzi M. Garcia - University of Illinois Urbana-ChampaignAnna Barwinska-Sendra - Newcastle UniversityEmma Tarrant - Newcastle UniversityEric P. Skaar - Vanderbilt University Medical CenterKevin J. Waldron - Newcastle UniversityThomas E. Kehl-Fie - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.13(1), pp.e1006125-e1006125
- Publisher
- Public Library Science
- DOI
- 10.1371/journal.ppat.1006125
- PMID
- 28103306
- PMCID
- PMC5245786
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Number of pages
- 19
- Grant note
- BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) March of Dimes 1369848 / Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) 098375/Z/12/Z / Wellcome Trust K22 AI104805; R01 AI118880; R01 AI101171 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Royal Society
- Language
- English
- Date published
- 01/01/2017
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618636102771
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