Journal article
The Metallophore Staphylopine Enables italic toggle="yes">Staphylococcus aureus /italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity
mBio, Vol.8(5), e01281-17
11/01/2017
DOI: 10.1128/mBio.01281-17
Abstract
ABSTRACT During infection, the host sequesters essential nutrients, such as zinc, to combat invading microbes. Despite the ability of the immune effector protein calprotectin to bind zinc with subpicomolar affinity, Staphylococcus aureus is able to successfully compete with the host for zinc. However, the zinc importers expressed by S. aureus remain unknown. Our investigations have revealed that S. aureus possesses two importers, AdcABC and CntABCDF, which are induced in response to zinc limitation. While AdcABC is similar to known zinc importers in other bacteria, CntABCDF has not previously been associated with zinc acquisition. Concurrent loss of the two systems severely impairs the ability of S. aureus to obtain zinc and grow in zinc-limited environments. Further investigations revealed that the Cnt system is responsible for the ability of S. aureus to compete with calprotectin for zinc in culture and contributes to acquisition of zinc during infection. The cnt locus also enables S. aureus to produce the broad-spectrum metallophore staphylopine. Similarly to the Cnt transporter, loss of staphylopine severely impairs the ability of S. aureus to resist host-imposed zinc starvation, both in culture and during infection. Further investigations revealed that together staphylopine and the Cnt importer function analogously to siderophore-based iron acquisition systems in order to facilitate zinc acquisition by S. aureus. Analogous systems are found in a broad range of Gram-positive and Gram-negative bacterial pathogens, suggesting that this new type of zinc importer broadly contributes to the ability of bacteria to cause infection. IMPORTANCE A critical host defense against infection is the restriction of zinc availability. Despite the subpicomolar affinity of the immune effector calprotectin for zinc, Staphylococcus aureus can successfully compete for this essential metal. Here, we describe two zinc importers, AdcABC and CntABCDF, possessed by S. aureus, the latter of which has not previously been associated with zinc acquisition. The ability of S. aureus to compete with the host for zinc is dependent on CntABCDF and the metallophore staphylopine, both in culture and during infection. These results expand the mechanisms utilized by bacteria to obtain zinc, beyond Adc-like systems, and demonstrate that pathogens utilize strategies similar to siderophore-based iron acquisition to obtain other essential metals during infection. The staphylopine synthesis machinery is present in a diverse collection of bacteria, suggesting that this new family of zinc importers broadly contributes to the ability of numerous pathogens to cause infection.
Details
- Title: Subtitle
- The Metallophore Staphylopine Enables italic toggle="yes">Staphylococcus aureus /italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity
- Creators
- Kyle P. Grim - University of Illinois Urbana-ChampaignBrian San Francisco - University of Illinois Urbana-ChampaignJana N. Radin - University of Illinois Urbana-ChampaignErin B. Brazel - University of AdelaideJessica L. Kelliher - University of Illinois Urbana-ChampaignPaola K. Párraga Solórzano - University of Illinois Urbana-ChampaignPhilip C. Kim - University of Illinois Urbana-ChampaignChristopher A. McDevitt - University of AdelaideThomas E. Kehl-Fie - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.8(5), e01281-17
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/mBio.01281-17
- eISSN
- 2150-7511
- Grant note
- name: Institute for Genomic Biology Post Doctoral Fellowship; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: K22 AI104805; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: R01 AI118880; DOI: 10.13039/501100000925, name: Department of Health | National Health and Medical Research Council, award: 1080784; DOI: 10.13039/501100000925, name: Department of Health | National Health and Medical Research Council, award: 1122582; DOI: 10.13039/501100000923, name: Australian Research Council, award: DP150104515; DOI: 10.13039/501100000923, name: Australian Research Council, award: DP170102102; DOI: 10.13039/100000912, name: March of Dimes Foundation
- Language
- English
- Date published
- 11/01/2017
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618640102771
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