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The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity

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 zi...

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Autores principales: Grim, Kyle P., San Francisco, Brian, Radin, Jana N., Brazel, Erin B., Kelliher, Jessica L., Párraga Solórzano, Paola K., Kim, Philip C., McDevitt, Christopher A., Kehl-Fie, Thomas E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666155/
https://www.ncbi.nlm.nih.gov/pubmed/29089427
http://dx.doi.org/10.1128/mBio.01281-17
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author Grim, Kyle P.
San Francisco, Brian
Radin, Jana N.
Brazel, Erin B.
Kelliher, Jessica L.
Párraga Solórzano, Paola K.
Kim, Philip C.
McDevitt, Christopher A.
Kehl-Fie, Thomas E.
author_facet Grim, Kyle P.
San Francisco, Brian
Radin, Jana N.
Brazel, Erin B.
Kelliher, Jessica L.
Párraga Solórzano, Paola K.
Kim, Philip C.
McDevitt, Christopher A.
Kehl-Fie, Thomas E.
author_sort Grim, Kyle P.
collection PubMed
description 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.
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spelling pubmed-56661552017-11-03 The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity Grim, Kyle P. San Francisco, Brian Radin, Jana N. Brazel, Erin B. Kelliher, Jessica L. Párraga Solórzano, Paola K. Kim, Philip C. McDevitt, Christopher A. Kehl-Fie, Thomas E. mBio Research Article 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. American Society for Microbiology 2017-10-31 /pmc/articles/PMC5666155/ /pubmed/29089427 http://dx.doi.org/10.1128/mBio.01281-17 Text en Copyright © 2017 Grim et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Grim, Kyle P.
San Francisco, Brian
Radin, Jana N.
Brazel, Erin B.
Kelliher, Jessica L.
Párraga Solórzano, Paola K.
Kim, Philip C.
McDevitt, Christopher A.
Kehl-Fie, Thomas E.
The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity
title The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity
title_full The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity
title_fullStr The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity
title_full_unstemmed The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity
title_short The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity
title_sort metallophore staphylopine enables staphylococcus aureus to compete with the host for zinc and overcome nutritional immunity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666155/
https://www.ncbi.nlm.nih.gov/pubmed/29089427
http://dx.doi.org/10.1128/mBio.01281-17
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