Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity

Kyle P Grim; Jana N Radin; Paola K Parraga Solorzano; Jacqueline R Morey; Katie A Frye; Katherine Ganio; Stephanie L Neville; Christopher A McDevitt; Thomas E Kehl-Fie

Journal article

Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity

Kyle P Grim, Jana N Radin, Paola K Parraga Solorzano, Jacqueline R Morey, Katie A Frye, Katherine Ganio, Stephanie L Neville, Christopher A McDevitt, Thomas E Kehl-Fie

JOURNAL OF BACTERIOLOGY | AMER SOC MICROBIOLOGY | Published : 2020

DOI: 10.1128/JB.00014-20

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 o..

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University of Melbourne Researchers

Katie Ganio Author Microbiology and Immunology

Christopher McDevitt Author Microbiology and Immunology

Stephanie Neville Author Microbiology and Immunology

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Grants

Awarded by National Institutes of Health

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by NHMRC

Awarded by Australian Research Council (ARC)

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported by a grant to T.E.K.-F. from the National Institutes of Health (R01 AI 118880) and a Vallee Scholar Award. This work was supported by National Health and Medical Research Council (NHMRC) project grants 1122582 and 1140554 to C.A.M. and an NHMRC Early Career Research Fellow (1142695) to S.L.N. This work was also supported by the Australian Research Council (ARC) Discovery project grant DP170102102 and Future Fellowship (FT170100006) to C.A.M.