Journal article
Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity
Journal of bacteriology, Vol.202(9), p.1
04/09/2020
DOI: 10.1128/JB.00014-20
PMCID: PMC7148132
PMID: 32071094
Abstract
The host restricts the availability of zinc to prevent infection. To overcome this defense, Staphylococcus aureus and Pseudomonas aeruginosa rely on zincophore-dependent zinc importers. Synthesis of the zincophore staphylopine by S. aureus and its import are both necessary for the bacterium to cause infection. In this study, we sought to elucidate how loss of zincophore efflux impacts bacterial resistance to host-imposed zinc starvation. In culture and during infection, mutants lacking CntE, the staphylopine efflux pump, were more sensitive to zinc starvation imposed by the metal-binding immune effector calprotectin than those lacking the ability to import staphylopine. However, disruption of staphylopine synthesis reversed the enhanced sensitivity phenotype of the Delta cntE mutant to calprotectin, indicating that intracellular toxicity of staphylopine is more detrimental than the impaired ability to acquire zinc. Unexpectedly, intracellular accumulation of staphylopine does not increase the expression of metal importers or alter cellular metal concentrations, suggesting that, contrary to prevailing models, the toxicity associated with staphylopine is not strictly due to intracellular chelation of metals. As P. aeruginosa and other pathogens produce zincophores with similar chemistry, our observations on the crucial importance of zincophore efflux are likely to be broadly relevant.
IMPORTANCE Staphylococcus aureus and many other bacterial pathogens rely on metal-binding small molecules to obtain the essential metal zinc during infection. In this study, we reveal that export of these small molecules is critical for overcoming host-imposed metal starvation during infection and prevents toxicity due to accumulation of the metal-binding molecule within the cell. Surprisingly, we found that intracellular toxicity of the molecule is not due to chelation of cellular metals.
Details
- Title: Subtitle
- Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity
- Creators
- Kyle P. Grim - University of Illinois Urbana-ChampaignJana N. Radin - University of Illinois Urbana-ChampaignPaola K. Parraga Solorzano - University of Illinois Urbana-ChampaignJacqueline R. Morey - University of Illinois Urbana-ChampaignKatie A. Frye - University of Illinois Urbana-ChampaignKatherine Ganio - Peter Doherty InstituteStephanie L. Neville - Peter Doherty InstituteChristopher A. McDevitt - Peter Doherty InstituteThomas E. Kehl-Fie - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- Journal of bacteriology, Vol.202(9), p.1
- Publisher
- Amer Soc Microbiology
- DOI
- 10.1128/JB.00014-20
- PMID
- 32071094
- PMCID
- PMC7148132
- ISSN
- 0021-9193
- eISSN
- 1098-5530
- Number of pages
- 16
- Grant note
- 1142695; 1140554 / National Health and Medical Research Council of Australia; National Health & Medical Research Council (NHMRC) of Australia DP170102102; FT170100006 / Australian Research Council (ARC); Australian Research Council 1142695 / NHMRC; National Health & Medical Research Council (NHMRC) of Australia R01 AI 118880 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Vallee Scholar Award 1122582; 1140554 / National Health and Medical Research Council (NHMRC); National Health & Medical Research Council (NHMRC) of Australia
- Language
- English
- Date published
- 04/09/2020
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618516902771
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