The Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity
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. Howeve...
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American Society for Microbiology
2017
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oai:doaj.org-article:8a26e45d09634efa9423ab852119bcc02021-11-15T15:51:51ZThe Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity10.1128/mBio.01281-172150-7511https://doaj.org/article/8a26e45d09634efa9423ab852119bcc02017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01281-17https://doaj.org/toc/2150-7511ABSTRACT 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.Kyle P. GrimBrian San FranciscoJana N. RadinErin B. BrazelJessica L. KelliherPaola K. Párraga SolórzanoPhilip C. KimChristopher A. McDevittThomas E. Kehl-FieAmerican Society for MicrobiologyarticleCntABCDFStaphylococcus aureuscalprotectinnutritional immunitysiderophoresstaphylopineMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017) |
| institution |
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DOAJ |
| language |
EN |
| topic |
CntABCDF Staphylococcus aureus calprotectin nutritional immunity siderophores staphylopine Microbiology QR1-502 |
| spellingShingle |
CntABCDF Staphylococcus aureus calprotectin nutritional immunity siderophores staphylopine Microbiology QR1-502 Kyle P. Grim Brian San Francisco Jana N. Radin Erin B. Brazel Jessica L. Kelliher Paola K. Párraga Solórzano Philip C. Kim Christopher A. McDevitt Thomas E. Kehl-Fie The Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity |
| description |
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. |
| format |
article |
| author |
Kyle P. Grim Brian San Francisco Jana N. Radin Erin B. Brazel Jessica L. Kelliher Paola K. Párraga Solórzano Philip C. Kim Christopher A. McDevitt Thomas E. Kehl-Fie |
| author_facet |
Kyle P. Grim Brian San Francisco Jana N. Radin Erin B. Brazel Jessica L. Kelliher Paola K. Párraga Solórzano Philip C. Kim Christopher A. McDevitt Thomas E. Kehl-Fie |
| author_sort |
Kyle P. Grim |
| title |
The Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity |
| title_short |
The Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity |
| title_full |
The Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity |
| title_fullStr |
The Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity |
| title_full_unstemmed |
The Metallophore Staphylopine Enables <italic toggle="yes">Staphylococcus aureus</italic> To Compete with the Host for Zinc and Overcome Nutritional Immunity |
| title_sort |
metallophore staphylopine enables <italic toggle="yes">staphylococcus aureus</italic> to compete with the host for zinc and overcome nutritional immunity |
| publisher |
American Society for Microbiology |
| publishDate |
2017 |
| url |
https://doaj.org/article/8a26e45d09634efa9423ab852119bcc0 |
| work_keys_str_mv |
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