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.

doi:10.1128/mbio.01281-17

Cited by 152Bacterial Genetics and BiotechnologyAntimicrobial Resistance in StaphylococcusTrace Elements in Health

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

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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. +1 more·2017·mBio

DOI 10.1128/mbio.01281-17PMC PMC5666155

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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.

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S. aureus produces and secretes staphylopine with broad metal chelating abilities.
“S. aureus produces and secretes staphylopine with broad metal chelating abilities 123,124 ,”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [124]

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Antibiotic resistance threats in the United States, 2019
(U.S.), C. F. D. C. A. P. (2019) · doi:10.15620/cdc:82532 · Cited by 5,782 · see citing works
Cytoscape 2.8: new features for data integration and network visualization
Smoot, M. E., Ono, K., Ruscheinski, J., Wang, P., & Ideker, T. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq675 · Cited by 4,770 · see citing works
Invasive Methicillin-Resistant <EMPH TYPE="ITAL">Staphylococcus aureus</EMPH> Infections in the United States
Klevens, R. M. (2007) · JAMA · doi:10.1001/jama.298.15.1763 · Cited by 3,726 · see citing works
Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans
Urban, C. F., Ermert, D., Schmid, M., Abed, U. A., Goosmann, C., Nacken, W. K. F., Brinkmann, V., Jungblut, P. R., & Zychlinsky, A. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000639 · Cited by 1,677 · see citing works
Nutritional immunity: transition metals at the pathogen–host interface
Hood, M. I., & Skaar, E. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2836 · Cited by 1,535 · see citing works
Metalloproteins and metal sensing
Waldron, K. J., Rutherford, J. C., Ford, D., & Robinson, N. J. (2009) · Nature · doi:10.1038/nature08300 · Cited by 1,269 · see citing works
Metal ions in biological catalysis: from enzyme databases to general principles
Andreini, C., Bertini, I., Cavallaro, G., Holliday, G. L., & Thornton, J. M. (2008) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-008-0404-5 · Cited by 1,150 · see citing works
Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers
Wertheim, H. F. L., Vos, M. D., Ott, A., van Belkum, A., Voß, A., Kluytmans, J. A. J. W., van Keulen, P. H. J., Vandenbroucke‐Grauls, C. M. J. E., Meester, M. H. M., & Verbrugh, H. A. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16897-9 · Cited by 891 · see citing works
Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses
Corbin, B. D., Seeley, E. H., Raab, A., Feldmann, J., Miller, M. R., Torres, V. J., Anderson, K. L., Dattilo, B. M., Dunman, P. M., Gerads, R., et al. (2008) · Science · doi:10.1126/science.1152449 · Cited by 857 · see citing works
Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks
Gerlt, J. A., Bouvier, J. T., Davidson, D. B., Imker, H. J., Sadkhin, B., Slater, D. R., & Whalen, K. L. (2015) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2015.04.015 · Cited by 805 · see citing works
S100A8 and S100A9 in inflammation and cancer
Gebhardt, C., Németh, J., Angel, P., & Hess, J. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.05.017 · Cited by 696 · see citing works
Zinc through the Three Domains of Life
Andreini, C., Banci, L., Bertini, I., & Rosato, A. (2006) · Journal of Proteome Research · doi:10.1021/pr0603699 · Cited by 648 · see citing works
Nutritional immunity beyond iron: a role for manganese and zinc
Kehl-Fie, T. E., & Skaar, E. P. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.11.008 · Cited by 634 · see citing works
Self-citation
Allelic replacement in Staphylococcus aureus with inducible counter-selection
Bae, T., & Schneewind, O. (2005) · Plasmid · doi:10.1016/j.plasmid.2005.05.005 · Cited by 624 · see citing works
A structural classification of substrate‐binding proteins
Berntsson, R. P. ‐., Smits, S. H. J., Schmitt, L., Slotboom, D.-J., & Poolman, B. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.04.043 · Cited by 552 · see citing works
Iron availability and infection
Weinberg, E. D. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.07.002 · Cited by 516 · see citing works
The ZnuABC high‐affinity zinc uptake system and its regulator Zur in Escherichia coli
Patzer, S. I., & Hantke, K. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00883.x · Cited by 490 · see citing works
Siderophores from Neighboring Organisms Promote the Growth of Uncultured Bacteria
Donofrio, A. E., Crawford, J. M., Stewart, E. J., Witt, K., Gavrish, E., Epstein, S. S., Clardy, J., & Lewis, K. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.02.010 · Cited by 457 · see citing works
Nutrient Metal Sequestration by Calprotectin Inhibits Bacterial Superoxide Defense, Enhancing Neutrophil Killing of Staphylococcus aureus
Kehl-Fie, T. E., Chitayat, S., Hood, M. I., Damo, S., Restrepo, N., Garcia, C., Munro, K. A., Chazin, W. J., & Skaar, E. P. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.07.004 · Cited by 419 · see citing works
Self-citation
Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens
Damo, S. M., Kehl-Fie, T. E., Sugitani, N., Holt, M. E., Rathi, S., Murphy, W. J., Zhang, Y., Betz, C., Hench, L., Fritz, G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220341110 · Cited by 388 · see citing works
Self-citation
Zinc Sequestration by the Neutrophil Protein Calprotectin Enhances Salmonella Growth in the Inflamed Gut
Liu, J. Z., Jellbauer, S., Poe, A. J., Ton, V., Pesciaroli, M., Kehl-Fie, T. E., Restrepo, N. A., Hosking, M. P., Edwards, R. A., Battistoni, A., et al. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.017 · Cited by 328 · see citing works
Self-citation
The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2
Fischbach, M. A., Lin, H., Zhou, L., Yu, Y., Abergel, R. J., Liu, D. R., Raymond, K. N., Wanner, B. L., Strong, R. K., Walsh, C. T., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604636103 · Cited by 319 · see citing works
Bacterial zinc uptake and regulators
Hantke, K. (2005) · Current Opinion in Microbiology · doi:10.1016/j.mib.2005.02.001 · Cited by 319 · see citing works
In Staphylococcus aureus , Fur Is an Interactive Regulator with PerR, Contributes to Virulence, and Is Necessary for Oxidative Stress Resistance through Positive Regulation of Catalase and Iron Homeostasis
Horsburgh, M. J., Ingham, E., & Foster, S. J. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.2.468-475.2001 · Cited by 316 · see citing works
Human calprotectin is an iron-sequestering host-defense protein
Nakashige, T. G., Zhang, B., Krebs, C., & Nolan, E. M. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1891 · Cited by 291 · see citing works
The Crystal Structure of the Human (S100A8/S100A9)2 Heterotetramer, Calprotectin, Illustrates how Conformational Changes of Interacting α-Helices Can Determine Specific Association of Two EF-hand Proteins
Korndörfer, I. P., Brueckner, F., & Skerra, A. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.04.065 · Cited by 278 · see citing works
Diverging roles of bacterial siderophores during infection
Holden, V. I., & Bachman, M. A. (2015) · Metallomics · doi:10.1039/c4mt00333k · Cited by 274 · cited 1× · see citing works
“In the context of infection, examples of the latter two strategies, which include siderophores and heme/hemoglobin transporters, have been largely restricted to the acquisition of Fe (32, 34).”
Background
Recent developments in understanding the iron acquisition strategies of gram positive pathogens
Sheldon, J. R., & Heinrichs, D. E. (2015) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuv009 · Cited by 272 · see citing works
Identification of an Acinetobacter baumannii Zinc Acquisition System that Facilitates Resistance to Calprotectin-mediated Zinc Sequestration
Hood, M. I., Mortensen, B. L., Moore, J. L., Zhang, Y., Kehl-Fie, T. E., Sugitani, N., Chazin, W. J., Caprioli, R. M., & Skaar, E. P. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003068 · Cited by 255 · see citing works
Self-citation
Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent
Bianchi, M., Niemiec, M. J., Siler, U., Urban, C. F., & Reichenbach, J. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.01.021 · Cited by 251 · see citing works
MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake
Horsburgh, M. J., Wharton, S. J., Cox, A. G., Ingham, E., Peacock, S., & Foster, S. J. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02944.x · Cited by 228 · see citing works
Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection
Minandri, F., Imperi, F., Frangipani, E., Bonchi, C., Visaggio, D., Facchini, M., Pasquali, P., Bragonzi, A., & Visca, P. (2016) · Infection and Immunity · doi:10.1128/iai.00098-16 · Cited by 228 · see citing works
Biosynthesis of a broad-spectrum nicotianamine-like metallophore in Staphylococcus aureus
Ghssein, G., Brutesco, C., Ouerdane, L., Fojcik, C., Izaute, A., Wang, S., Hajjar, C., Lobinski, R., Lemaire, D., Richaud, P., et al. (2016) · Science · doi:10.1126/science.aaf1018 · Cited by 227 · see citing works
Nickel Homeostasis and Nickel Regulation: An Overview
Li, Y., & Zamble, D. B. (2009) · Chemical Reviews · doi:10.1021/cr900010n · Cited by 217 · see citing works
MntABC and MntH Contribute to Systemic Staphylococcus aureus Infection by Competing with Calprotectin for Nutrient Manganese
Kehl-Fie, T. E., Zhang, Y., Moore, J. L., Farrand, A. J., Hood, M. I., Rathi, S., Chazin, W. J., Caprioli, R. M., & Skaar, E. P. (2013) · Infection and Immunity · doi:10.1128/iai.00420-13 · Cited by 213 · see citing works
Self-citation
Calprotectin‐Mediated Zinc Chelation as a Biostatic Mechanism in Host Defence
Clohessy, P. A., & Golden, B. E. (1995) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1995.tb03695.x · Cited by 210 · see citing works
Anthrax pathogen evades the mammalian immune system through stealth siderophore production
Abergel, R. J., Wilson, M. K., Arceneaux, J. E. L., Hoette, T. M., Strong, R. K., Byers, B. R., & Raymond, K. N. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607055103 · Cited by 198 · see citing works
Fluorescent reporters for Staphylococcus aureus
Malone, C. L., Boles, B. R., Lauderdale, K. J., Thoendel, M., Kavanaugh, J. S., & Horswill, A. R. (2009) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2009.02.011 · Cited by 193 · see citing works
An improved tetracycline-inducible expression vector for Staphylococcus aureus
Corrigan, R. M., & Foster, T. J. (2008) · Plasmid · doi:10.1016/j.plasmid.2008.10.001 · Cited by 188 · see citing works
Calcium Ion Gradients Modulate the Zinc Affinity and Antibacterial Activity of Human Calprotectin
Brophy, M. B., Hayden, J. A., & Nolan, E. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja307974e · Cited by 156 · see citing works
Contribution of the Shigella flexneri Sit, Iuc, and Feo Iron Acquisition Systems to Iron Acquisition In Vitro and in Cultured Cells
Runyen-Janecky, L. J., Reeves, S. A., Gonzales, E. G., & Payne, S. M. (2003) · Infection and Immunity · doi:10.1128/iai.71.4.1919-1928.2003 · Cited by 155 · see citing works
The <scp>S</scp> taphylococcus aureus <scp> <scp>Opp1</scp> ABC </scp> transporter imports nickel and cobalt in zinc‐depleted conditions and contributes to virulence
Remy, L., Carrière, M., Derré‐Bobillot, A., Martini, C., Sanguinetti, M., & Borezée‐Durant, E. (2013) · Molecular Microbiology · doi:10.1111/mmi.12126 · Cited by 139 · see citing works
ZnuA and zinc homeostasis in Pseudomonas aeruginosa
Pederick, V. G., Eijkelkamp, B. A., Begg, S. L., Ween, M. P., McAllister, L. J., Paton, J. C., & McDevitt, C. A. (2015) · Scientific Reports · doi:10.1038/srep13139 · Cited by 138 · see citing works
Self-citation
Imperfect coordination chemistry facilitates metal ion release in the Psa permease
Couñago, R. M., Ween, M. P., Neville, S. L., Bajaj, M., Zuegg, J., O’Mara, M. L., Cooper, M. A., McEwan, A. G., Paton, J. C., Kobe, B., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1382 · Cited by 137 · see citing works
Self-citation
Zinc uptake by Streptococcus pneumoniae depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence: Zinc uptake of Streptococcus pneumoniae
Bayle, L., Chimalapati, S., Schoehn, G., Brown, J., Vernet, T., & Durmort, C. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07862.x · Cited by 137 · see citing works
Myeloid-Related Protein-14 Contributes to Protective Immunity in Gram-Negative Pneumonia Derived Sepsis
Achouiti, A., Vogl, T., Urban, C. F., Röhm, M., Hommes, T. J., van Zoelen, M. A. D., Florquin, S., Roth, J., van 't Veer, C., de Vos, A. F., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002987 · Cited by 135 · see citing works
The Zur-Regulated ZinT Protein Is an Auxiliary Component of the High-Affinity ZnuABC Zinc Transporter That Facilitates Metal Recruitment during Severe Zinc Shortage
Petrarca, P., Ammendola, S., Pasquali, P., & Battistoni, A. (2010) · Journal of Bacteriology · doi:10.1128/jb.01310-09 · Cited by 129 · see citing works
Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae
Neville, S. L., Eijkelkamp, B. A., Luo, Z., Couñago, R. M., Morey, J. R., Maher, M. J., Ong, C. Y., McEwan, A. G., Kobe, B., O’Mara, M. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms7418 · Cited by 128 · see citing works
Self-citation
High-Affinity Manganese Coordination by Human Calprotectin Is Calcium-Dependent and Requires the Histidine-Rich Site Formed at the Dimer Interface
Hayden, J. A., Brophy, M. B., Cunden, L. S., & Nolan, E. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3096416 · Cited by 128 · see citing works
A Superoxide Dismutase Capable of Functioning with Iron or Manganese Promotes the Resistance of Staphylococcus aureus to Calprotectin and Nutritional Immunity
Garcia, Y. M., Barwinska‐Sendra, A., Tarrant, E., Skaar, E. P., Waldron, K. J., & Kehl‐Fie, T. E. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006125 · Cited by 124 · see citing works
Self-citation
Roles of the Extraintestinal Pathogenic Escherichia coli ZnuACB and ZupT Zinc Transporters during Urinary Tract Infection
Sabri, M., Houle, S., & Dozois, C. M. (2009) · Infection and Immunity · doi:10.1128/iai.01082-08 · Cited by 118 · see citing works
Role and regulation of heme iron acquisition in gram-negative pathogens
Runyen-Janecky, L. J. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00055 · Cited by 117 · see citing works
Mammalian Siderophores, Siderophore-binding Lipocalins, and the Labile Iron Pool
Correnti, C., & Strong, R. K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.311829 · Cited by 115 · see citing works
Competition for zinc binding in the host-pathogen interaction
Cerasi, M., Ammendola, S., & Battistoni, A. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00108 · Cited by 111 · see citing works
The role of ATP-binding cassette transporters in bacterial pathogenicity
Lewis, V. G., Ween, M. P., & McDevitt, C. A. (2012) · PROTOPLASMA · doi:10.1007/s00709-011-0360-8 · Cited by 110 · see citing works
Self-citation
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Grossoehme, N., Kehl-Fie, T. E., Ma, Z., Adams, K. W., Cowart, D. M., Scott, R. A., Skaar, E. P., & Giedroc, D. P. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.220012 · Cited by 101 · see citing works
Self-citation
AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in S treptococcus pneumoniae
Plumptre, C. D., Eijkelkamp, B. A., Morey, J. R., Behr, F. M., Couñago, R. M., Ogunniyi, A. D., Kobe, B., O’Mara, M. L., Paton, J. C., & McDevitt, C. A. (2013) · Molecular Microbiology · doi:10.1111/mmi.12504 · Cited by 99 · see citing works
Self-citation
A nickel ABC-transporter of Staphylococcus aureus is involved in urinary tract infection: Nickel uptake and virulence in Staphylococcus aureus
Hiron, A., Posteraro, B., Carrière, M., Remy, L., Delporte, C., La Sorda, M., Sanguinetti, M., Juillard, V., & Borezée-Durant, E. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07287.x · Cited by 97 · see citing works
Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks
Zhao, S., Sakai, A., Zhang, X., Vetting, M. W., Kumar, R., Hillerich, B., Francisco, B. S., Solbiati, J., Steves, A., Brown, S. D., et al. (2014) · eLife · doi:10.7554/elife.03275 · Cited by 93 · see citing works
The Host Protein Calprotectin Modulates the Helicobacter pylori cag Type IV Secretion System via Zinc Sequestration
Gaddy, J. A., Radin, J. N., Loh, J. T., Piazuelo, M. B., Kehl-Fie, T. E., Delgado, A. G., Ilca, F. T., Peek, R. M., Cover, T. L., Chazin, W. J., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004450 · Cited by 87 · see citing works
Self-citation
zur: a Zn2+-responsive regulatory element of Staphylococcus aureus The GenBank accession number for the sequence reported in this paper is AF101263.
Lindsay, J. A., & Foster, S. J. (2001) · Microbiology · doi:10.1099/00221287-147-5-1259 · Cited by 84 · see citing works
Znu Is the Predominant Zinc Importer in Yersinia pestis during In Vitro Growth but Is Not Essential for Virulence
Desrosiers, D. C., Bearden, S. W., Mier, I., Abney, J., Paulley, J. T., Fetherston, J. D., Salazar, J. C., Radolf, J. D., & Perry, R. D. (2010) · Infection and Immunity · doi:10.1128/iai.00732-10 · Cited by 78 · see citing works
The Two-Component System ArlRS and Alterations in Metabolism Enable Staphylococcus aureus to Resist Calprotectin-Induced Manganese Starvation
Radin, J. N., Kelliher, J. L., Solórzano, P. K. P., & Kehl‐Fie, T. E. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1006040 · Cited by 77 · see citing works
Self-citation
Two Zinc Uptake Systems Contribute to the Full Virulence of Listeria monocytogenes during Growth In Vitro and In Vivo
Corbett, D., Wang, J., Schuler, S., Lopez-Castejon, G., Glenn, S., Brough, D., Andrew, P. W., Cavet, J. S., & Roberts, I. S. (2012) · Infection and Immunity · doi:10.1128/iai.05904-11 · Cited by 71 · see citing works
Acinetobacter baumannii Coordinates Urea Metabolism with Metal Import To Resist Host-Mediated Metal Limitation
Juttukonda, L. J., Chazin, W., & Skaar, E. P. (2016) · mBio · doi:10.1128/mbio.01475-16 · Cited by 71 · see citing works
A novel siderophore system is essential for the growth of Pseudomonas aeruginosa in airway mucus
Gi, M., Lee, K., Kim, S. C., Yoon, J., Yoon, S. S., & Choi, J. Y. (2015) · Scientific Reports · doi:10.1038/srep14644 · Cited by 70 · see citing works
The capability of Pseudomonas aeruginosa to recruit zinc under conditions of limited metal availability is affected by inactivation of the ZnuABC transporter
D’Orazio, M., Mastropasqua, M. C., Cerasi, M., Pacello, F., Consalvo, A., Chirullo, B., Mortensen, B. L., Skaar, E. P., Ciavardelli, D., Pasquali, P., et al. (2015) · Metallomics · doi:10.1039/c5mt00017c · Cited by 68 · see citing works
Siderophore Cross-Utilization Amongst Rhizospheric Bacteria and the Role of Their Differential Affinities for Fe3+ on Growth Stimulation Under Iron-Limited Conditions
Joshi, F. R., Archana, G., & Desai, A. J. (2006) · Current Microbiology · doi:10.1007/s00284-005-0400-8 · Cited by 64 · see citing works
Characterization of Zur-dependent genes and direct Zur targets in Yersinia pestis
Li, Y., Qiu, Y., Gao, H., Guo, Z., Han, Y., Song, Y., Du, Z., Wang, X., Zhou, D., & Yang, R. (2009) · BMC Microbiology · doi:10.1186/1471-2180-9-128 · Cited by 63 · see citing works
The Hexahistidine Motif of Host-Defense Protein Human Calprotectin Contributes to Zinc Withholding and Its Functional Versatility
Nakashige, T. G., Stephan, J. R., Cunden, L. S., Brophy, M. B., Wommack, A. J., Keegan, B. C., Shearer, J., & Nolan, E. M. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b06845 · Cited by 56 · see citing works
Manganese transporters Yfe and MntH are Fur-regulated and important for the virulence of Yersinia pestis
Perry, R. D., Craig, S. K., Abney, J., Bobrov, A. G., Kirillina, O., Mier, I., Truszczynska, H., & Fetherston, J. D. (2012) · Microbiology · doi:10.1099/mic.0.053710-0 · Cited by 50 · see citing works
Staphylococcus aureus NorD, a Putative Efflux Pump Coregulated with the Opp1 Oligopeptide Permease, Contributes Selectively to Fitness In Vivo
Ding, Y., Fu, Y., Lee, J. C., & Hooper, D. C. (2012) · Journal of Bacteriology · doi:10.1128/jb.01414-12 · Cited by 50 · see citing works
Dual Zinc Transporter Systems in Vibrio cholerae Promote Competitive Advantages over Gut Microbiome
Sheng, Y., Fan, F., Jensen, O., Zhong, Z., Kan, B., Wang, H., & Zhu, J. (2015) · Infection and Immunity · doi:10.1128/iai.00447-15 · Cited by 48 · see citing works
Promiscuous Nickel Import in Human Pathogens: Structure, Thermodynamics, and Evolution of Extracytoplasmic Nickel-Binding Proteins
Lebrette, H., Brochier‐Armanet, C., Zambelli, B., Reuse, H. D., Borezée‐Durant, E., Ciurli, S., & Cavazza, C. (2014) · Structure · doi:10.1016/j.str.2014.07.012 · Cited by 40 · see citing works
Nickel recognition by bacterial importer proteins
Chivers, P. T. (2015) · Metallomics · doi:10.1039/c4mt00310a · Cited by 32 · see citing works
Growth promotion of the opportunistic human pathogen, Staphylococcus lugdunensis , by heme, hemoglobin, and coculture with Staphylococcus aureus
Brozyna, J. R., Sheldon, J. R., & Heinrichs, D. E. (2014) · MicrobiologyOpen · doi:10.1002/mbo3.162 · Cited by 31 · see citing works
Multiple ABC transporters are involved in the acquisition of petrobactin in Bacillus anthracis
Dixon, S. D., Janes, B. K., Bourgis, A. E. T., Carlson, P. E., & Hanna, P. C. (2012) · Molecular Microbiology · doi:10.1111/j.1365-2958.2012.08028.x · Cited by 19 · see citing works

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Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701 · see citing works
The Role of Macrophages in Staphylococcus aureus Infection
Pidwill, G. R., Gibson, J. F., Cole, J., Renshaw, S. A., & Foster, S. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.620339 · Cited by 342 · see citing works
Transition Metal Sequestration by the Host-Defense Protein Calprotectin
Zygiel, E. M., & Nolan, E. M. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012312 · Cited by 187 · see citing works
Nutrient Zinc at the Host–Pathogen Interface
Lonergan, Z. R., & Skaar, E. P. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.06.010 · Cited by 129 · see citing works
S-Adenosylmethionine: more than just a methyl donor
Lee, Y., Ren, D., Jeon, B., & Liu, H. (2023) · Natural Product Reports · doi:10.1039/d2np00086e · Cited by 128 · see citing works
RsaC sRNA modulates the oxidative stress response of Staphylococcus aureus during manganese starvation
Lalaouna, D., Baude, J., Wu, Z., Tomasini, A., Chicher, J., Marzi, S., Vandenesch, F., Romby, P., Caldelari, I., & Moreau, K. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz728 · Cited by 114 · see citing works
The role of metal ions in the virulence and viability of bacterial pathogens
Neville, S. L. (2019) · Biochemical Society Transactions · doi:10.1042/bst20180275 · Cited by 114 · see citing works
Zinc: Multidimensional Effects on Living Organisms
Cuajungco, M. P., Ramirez, M. S., & Tolmasky, M. E. (2021) · Biomedicines · doi:10.3390/biomedicines9020208 · Cited by 105 · see citing works
Metal binding ability of microbial natural metal chelators and potential applications
Hofmann, M., Retamal-Morales, G., & Tischler, D. (2020) · Natural Product Reports · doi:10.1039/c9np00058e · Cited by 92 · see citing works
Mechanistic insights into staphylopine-mediated metal acquisition
Song, L., Zhang, Y., Chen, W., Gu, T., Zhang, S., & Ji, Q. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718382115 · Cited by 71 · see citing works
Staphylococcal diversity in atopic dermatitis from an individual to a global scale
Kashaf, S. S., Harkins, C. P., Deming, C., Joglekar, P., Conlan, S., Holmes, C. J., Almeida, A., Finn, R. D., Segre, J. A., & Kong, H. H. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.03.010 · Cited by 69 · see citing works
The Key Element Role of Metallophores in the Pathogenicity and Virulence of Staphylococcus aureus: A Review
Ghssein, G., & Ezzeddine, Z. (2022) · Biology · doi:10.3390/biology11101525 · Cited by 66 · see citing works
Virulence and Metabolism
Richardson, A. R. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.gpp3-0011-2018 · Cited by 61 · see citing works
Genetic Regulation of Metal Ion Homeostasis in Staphylococcus aureus
Price, E. E., & Boyd, J. M. (2020) · Trends in Microbiology · doi:10.1016/j.tim.2020.04.004 · Cited by 59 · see citing works
Role of Nickel in Microbial Pathogenesis
Maier, R. J., & Benoit, S. L. (2019) · Inorganics · doi:10.3390/inorganics7070080 · Cited by 63 · see citing works
The Acinetobacter baumannii Znu System Overcomes Host-Imposed Nutrient Zinc Limitation
Hesse, L. E., Lonergan, Z. R., Beavers, W. N., & Skaar, E. P. (2019) · Infection and Immunity · doi:10.1128/iai.00746-19 · Cited by 59 · see citing works
Pseudomonas aeruginosa zinc homeostasis: Key issues for an opportunistic pathogen
Gonzalez, M. R., Ducret, V., Leoni, S., & Perron, K. (2018) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2018.01.018 · Cited by 57 · see citing works
Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking
Capdevila, D. A., Rondón, J. J., Edmonds, K. A., Rocchio, J. S., Dujovne, M. V., & Giedroc, D. P. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00264 · Cited by 59 · see citing works
The Staphylococcus aureus Transcriptome during Cystic Fibrosis Lung Infection
Ibberson, C. B., & Whiteley, M. (2019) · mBio · doi:10.1128/mbio.02774-19 · Cited by 55 · see citing works
Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts
Price, S. L., Vadyvaloo, V., DeMarco, J. K., Brady, A., Gray, P. A., Kehl-Fie, T. E., Garneau-Tsodikova, S., Perry, R. D., & Lawrenz, M. B. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2104073118 · Cited by 49 · see citing works
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Bioinformatic Mapping of Opine-Like Zincophore Biosynthesis in Bacteria
Morey, J. R., & Kehl‐Fie, T. E. (2020) · mSystems · doi:10.1128/msystems.00554-20 · Cited by 51 · see citing works
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Zur: Zinc-Sensing Transcriptional Regulator in a Diverse Set of Bacterial Species
Kandari, D., Joshi, H., & Bhatnagar, R. (2021) · Pathogens · doi:10.3390/pathogens10030344 · Cited by 46 · see citing works
Identification of Zinc-Dependent Mechanisms Used by Group B Streptococcus To Overcome Calprotectin-Mediated Stress
Burcham, L. R., Le Breton, Y., Radin, J. N., Spencer, B. L., Deng, L., Hiron, A., Ransom, M. R., Mendonça, J. D. C., Belew, A. T., El-Sayed, N. M., et al. (2020) · mBio · doi:10.1128/mbio.02302-20 · Cited by 47 · see citing works
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Kupyaphores are zinc homeostatic metallophores required for colonization of Mycobacterium tuberculosis
Mehdiratta, K., Singh, S., Sharma, S., Bhosale, R. S., Choudhury, R., Masal, D. P., Manocha, A., Dhamale, B. D., Khan, N. A., Vivekanand, A., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2110293119 · Cited by 47 · see citing works
Independent and cooperative regulation of staphylopine biosynthesis and trafficking by Fur and Zur
Fojcik, C., Arnoux, P., Ouerdane, L., Aigle, M., Alfonsi, L., & Borezée‐Durant, E. (2018) · Molecular Microbiology · doi:10.1111/mmi.13927 · Cited by 43 · see citing works
Multi-metal nutrient restriction and crosstalk in metallostasis systems in microbial pathogens
Jordan, M. R., Wang, J., Capdevila, D. A., & Giedroc, D. P. (2020) · Current Opinion in Microbiology · doi:10.1016/j.mib.2020.01.010 · Cited by 44 · see citing works
Staphylopine, pseudopaline, and yersinopine dehydrogenases: A structural and kinetic analysis of a new functional class of opine dehydrogenase
McFarlane, J. S., Davis, C. L., & Lamb, A. L. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002007 · Cited by 43 · see citing works
COG0523 proteins: a functionally diverse family of transition metal-regulated G3E P-loop GTP hydrolases from bacteria to man
Edmonds, K. A., Jordan, M. R., & Giedroc, D. P. (2021) · Metallomics · doi:10.1093/mtomcs/mfab046 · Cited by 44 · see citing works
Synergy between Nutritional Immunity and Independent Host Defenses Contributes to the Importance of the MntABC Manganese Transporter during Staphylococcus aureus Infection
Radin, J. N., Zhu, J., Brazel, E. B., McDevitt, C. A., & Kehl‐Fie, T. E. (2018) · Infection and Immunity · doi:10.1128/iai.00642-18 · Cited by 41 · see citing works
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The ancient roots of nicotianamine: diversity, role, regulation and evolution of nicotianamine-like metallophores
Laffont, C., & Arnoux, P. (2020) · Metallomics · doi:10.1039/d0mt00150c · Cited by 41 · see citing works
Mechanistic Insights into the Metal-Dependent Activation of ZnII-Dependent Metallochaperones
Jordan, M. R., Wang, J., Weiss, A., Skaar, E. P., Capdevila, D. A., & Giedroc, D. P. (2019) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.9b01173 · Cited by 39 · see citing works
Systematic identification of molecular mediators of interspecies sensing in a community of two frequently coinfecting bacterial pathogens
Zarrella, T. M., & Khare, A. (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001679 · Cited by 31 · see citing works
Iron Acquisition by Bacterial Pathogens: Beyond Tris‐Catecholate Complexes
Zhang, Y., Sen, S., & Giedroc, D. P. (2020) · ChemBioChem · doi:10.1002/cbic.201900778 · Cited by 30 · see citing works
Secondary Metabolites Governing Microbiome Interaction of Staphylococcal Pathogens and Commensals
Salazar, B. O. T., Heilbronner, S., Peschel, A., & Krismer, B. (2021) · Microbial Physiology · doi:10.1159/000517082 · Cited by 28 · see citing works
Disruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureus
Solórzano, P. K. P., Yao, J., Rock, C. O., & Kehl‐Fie, T. E. (2019) · mBio · doi:10.1128/mbio.01321-19 · Cited by 30 · see citing works
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Strategies for Zinc Uptake in Pseudomonas aeruginosa at the Host–Pathogen Interface
Wang, S., Cheng, J., Yanting, N., Li, P., Zhang, X., & Lin, J. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.741873 · Cited by 26 · see citing works
The Yersinia High-Pathogenicity Island Encodes a Siderophore-Dependent Copper Response System in Uropathogenic Escherichia coli
Katumba, G. L., Tran, H., & Henderson, J. P. (2022) · mBio · doi:10.1128/mbio.02391-21 · Cited by 27 · see citing works
Calprotectin-Mediated Zinc Chelation Inhibits Pseudomonas aeruginosa Protease Activity in Cystic Fibrosis Sputum
Vermilyea, D. M., Crocker, A. W., Gifford, A. H., & Hogan, D. A. (2021) · Journal of Bacteriology · doi:10.1128/jb.00100-21 · Cited by 24 · see citing works
Inhibition of Isoleucyl-tRNA Synthetase by the Hybrid Antibiotic Thiomarinol
Johnson, R. A., Chan, A. N., Ward, R. D., McGlade, C. A., Hatfield, B. M., Peters, J. M., & Ли, Б. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c02622 · Cited by 26 · see citing works
Simple rules govern the diversity of bacterial nicotianamine-like metallophores
Laffont, C., Brutesco, C., Hajjar, C., Cullia, G., Fanelli, R., Ouerdane, L., Cavelier, F., & Arnoux, P. (2019) · Biochemical Journal · doi:10.1042/bcj20190384 · Cited by 26 · see citing works
How Zinc-Binding Systems, Expressed by Human Pathogens, Acquire Zinc from the Colonized Host Environment: A Critical Review on Zincophores
Remelli, M., Bellotti, D., & Rowińska‐Żyrek, M. (2021) · Current Medicinal Chemistry · doi:10.2174/1389200222666210514012945 · Cited by 24 · see citing works
The AdcACB/AdcAII system is essential for zinc homeostasis and an important contributor of Enterococcus faecalis virulence
(2022) · doi:10.1080/21505594.2022.2056965 · Cited by 23 · see citing works
Effect of Ferredoxin Receptor FusA on the Virulence Mechanism of Pseudomonas plecoglossicida
He, R., Wang, J., Lin, M., Tian, J., Wu, B. J., Tan, X., Zhou, J., Zhang, J., Yan, Q., & Huang, L. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.808800 · Cited by 23 · see citing works
Intracellular accumulation of staphylopine impairs the fitness of Staphylococcus aureus cntE mutant
Chen, C., & Hooper, D. C. (2019) · FEBS Letters · doi:10.1002/1873-3468.13396 · Cited by 22 · see citing works
Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity
Grim, K. P., Radin, J. N., Solórzano, P. K. P., Morey, J. R., Frye, K. A., Ganio, K., Neville, S. L., McDevitt, C. A., & Kehl‐Fie, T. E. (2020) · Journal of Bacteriology · doi:10.1128/jb.00014-20 · Cited by 22 · see citing works
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Through the Looking Glass: Chiral Recognition of Substrates and Products at the Active Sites of Racemases and Epimerases
Bearne, S. L. (2020) · Chemistry - A European Journal · doi:10.1002/chem.201905826 · Cited by 22 · see citing works
Calprotectin (S100A8/A9) Is an Innate Immune Effector in Experimental Periodontitis
Johnstone, K. F., Wei, Y., Bittner‐Eddy, P. D., Vreeman, G. W., Stone, I. A., Clayton, J. B., Reilly, C., Walbon, T. B., Wright, E. N., Hoops, S., et al. (2021) · Infection and Immunity · doi:10.1128/iai.00122-21 · Cited by 21 · see citing works
Control by Metals of Staphylopine Dehydrogenase Activity during Metallophore Biosynthesis
Hajjar, C., Fanelli, R., Laffont, C., Brutesco, C., Cullia, G., Tribout, M., Nurizzo, D., Borezée‐Durant, E., Voulhoux, R., Pignol, D., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b01676 · Cited by 21 · see citing works
A Manganese-independent Aldolase Enables Staphylococcus aureus To Resist Host-imposed Metal Starvation
Solórzano, P. K. P., Bastille, T. S., Radin, J. N., & Kehl‐Fie, T. E. (2023) · mBio · doi:10.1128/mbio.03223-22 · Cited by 20 · see citing works
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Resisting death by metal: metabolism and Cu/Zn homeostasis in bacteria
Sullivan, M. J., Terán, I., Goh, K. G. K., & Ulett, G. C. (2024) · Emerging Topics in Life Sciences · doi:10.1042/etls20230115 · Cited by 21 · see citing works
Two ABC Transporters and a Periplasmic Metallochaperone Participate in Zinc Acquisition in Paracoccus denitrificans
Neupane, D. P., Kumar, S., & Yukl, E. T. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00854 · Cited by 21 · see citing works
Crystal structure of CntK, the cofactor-independent histidine racemase in staphylopine-mediated metal acquisition of Staphylococcus aureus
Luo, S., Ju, Y., Zhou, J., Gu, Q., Xu, J., & Zhou, H. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.05.169 · Cited by 21 · see citing works
Occurrence of D-amino acids in natural products
Armstrong, D. W., & Berthod, A. (2023) · Natural Products and Bioprospecting · doi:10.1007/s13659-023-00412-0 · Cited by 20 · see citing works
Metal sequestration by S100 proteins in chemically diverse environments
Rosen, T., Wang, K.-K. A., & Nolan, E. M. (2022) · Trends in Microbiology · doi:10.1016/j.tim.2021.12.006 · Cited by 19 · see citing works
Battle for Metals: Regulatory RNAs at the Front Line
Charbonnier, M., González-Espinoza, G., Kehl‐Fie, T. E., & Lalaouna, D. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.952948 · Cited by 19 · see citing works
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Increased flexibility in the use of exogenous lipoic acid by Staphylococcus aureus
Laczkovich, I., Teoh, W. P., Flury, S., Grayczyk, J. P., Zorzoli, A., & Alonzo, F. (2018) · Molecular Microbiology · doi:10.1111/mmi.13970 · Cited by 19 · see citing works
Zinc binding proteome of a phytopathogen Xanthomonas translucens pv. undulosa
Sharma, A., Sharma, D., & Verma, S. K. (2019) · Royal Society Open Science · doi:10.1098/rsos.190369 · Cited by 19 · see citing works
Coordinated adaptation of Staphylococcus aureus to calprotectin-dependent metal sequestration
Ruiz, V. M. R., Freiberg, J. A., Weiss, A., Green, E. R., Jobson, M.-E., Felton, E. A., Shaw, L. N., Chazin, W., & Skaar, E. P. (2024) · mBio · doi:10.1128/mbio.01389-24 · Cited by 18 · see citing works
Peptidomimetics – An infinite reservoir of metal binding motifs in metabolically stable and biologically active molecules
Wątły, J., Miller, A., Kozłowski, H., & Rowińska‐Żyrek, M. (2021) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2021.111386 · Cited by 18 · see citing works
Genomic Analyses Identify Manganese Homeostasis as a Driver of Group B Streptococcal Vaginal Colonization
Burcham, L. R., Akbari, M. S., Alhajjar, N., Keogh, R. A., Radin, J. N., Kehl‐Fie, T. E., Belew, A. T., El-Sayed, N. M., McIver, K. S., & Doran, K. S. (2022) · mBio · doi:10.1128/mbio.00985-22 · Cited by 18 · see citing works
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Staphylococcus aureus metal acquisition in the mastitic mammary gland
Carlson, S. K., Erickson, D. L., & Wilson, E. (2020) · Microbial Pathogenesis · doi:10.1016/j.micpath.2020.104179 · Cited by 17 · see citing works
A Small-Molecule Modulator of Metal Homeostasis in Gram-Positive Pathogens
Juttukonda, L. J., Beavers, W. N., Unsihuay, D., Kim, K., Pishchany, G., Horning, K. J., Weiss, A., Al‐Tameemi, H., Boyd, J. M., Sulikowski, G. A., et al. (2020) · mBio · doi:10.1128/mbio.02555-20 · Cited by 17 · see citing works
Staphylopine and pseudopaline dehydrogenase from bacterial pathogens catalyze reversible reactions and produce stereospecific metallophores
McFarlane, J. S., Zhang, J., Wang, S., Lei, X., Moran, G. R., & Lamb, A. L. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011059 · Cited by 17 · see citing works
Host subversion of bacterial metallophore usage drives copper intoxication
Hossain, S., Morey, J. R., Neville, S. L., Ganio, K., Radin, J. N., Norambuena, J., Boyd, J. M., McDevitt, C. A., & Kehl‐Fie, T. E. (2023) · mBio · doi:10.1128/mbio.01350-23 · Cited by 16 · see citing works
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Comparative Transcriptomic Analysis of Staphylococcus aureus Associated with Periprosthetic Joint Infection under in Vivo and in Vitro Conditions
Masters, T. L., Johnson, S. P., Jeraldo, P., Greenwood‐Quaintance, K. E., Cunningham, S. A., Abdel, M. P., Chia, N., & Patel, R. (2021) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2021.05.011 · Cited by 16 · see citing works
The Sensor Histidine Kinase ArlS Is Necessary for Staphylococcus aureus To Activate ArlR in Response to Nutrient Availability
Solórzano, P. K. P., Shupe, A. C., & Kehl-Fie, T. E. (2021) · Journal of Bacteriology · doi:10.1128/jb.00422-21 · Cited by 16 · see citing works
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Fpa (YlaN) is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression in Staphylococcus aureus
Boyd, J. M., Ryan Kaler, K., Esquilín-Lebrón, K., Pall, A., Campbell, C. J., Foley, M. E., Rios-Delgado, G., Mustor, E. M., Stephens, T. G., Bovermann, H., et al. (2024) · mBio · doi:10.1128/mbio.02310-24 · Cited by 14 · see citing works
A Trap-Door Mechanism for Zinc Acquisition by Streptococcus pneumoniae AdcA
Luo, Z., Morey, J. R., Deplazes, E., Motygullina, A., Tan, A., Ganio, K., Neville, S. L., Eleftheriadis, N., Isselstein, M., Pederick, V. G., et al. (2021) · mBio · doi:10.1128/mbio.01958-20 · Cited by 15 · see citing works
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The Extracellular Metallometabolome: Metallophores, Metal Ionophores, and Other Chelating Agents as Natural Products
Maret, W. (2024) · Natural Product Communications · doi:10.1177/1934578x241271701 · Cited by 14 · see citing works
Dysbiosis and diabetic foot ulcers: A metabolic perspective of Staphylococcus aureus infection
Liu, R., Feng, J., Ni, Y., Chen, K., Wang, Y., Zhang, T., Zhou, M., & Zhao, C. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117498 · Cited by 14 · see citing works
Intergenic evolution during host adaptation increases expression of the metallophore pseudopaline in Pseudomonas aeruginosa
Hermansen, G. M. M., Hansen, M. L., Khademi, S. M. H., & Jelsbak, L. (2018) · Microbiology · doi:10.1099/mic.0.000687 · Cited by 13 · see citing works
Staphylopine dehydrogenase in the apo state
Hajjar, C., & Arnoux, P. (2018) · Worldwide Protein Data Bank · doi:10.2210/pdb6h31/pdb · Cited by 13 · see citing works
Transition metals and Enterococcus faecalis: Homeostasis, virulence and perspectives
Ali, I. A. A., Cheung, G. S. P., & Neelakantan, P. (2022) · Molecular Oral Microbiology · doi:10.1111/omi.12391 · Cited by 12 · see citing works
How Staphylococcus aureus and Pseudomonas aeruginosa Hijack the Host Immune Response in the Context of Cystic Fibrosis
Souche, A., Vandenesch, F., Doléans-Jordheim, A., & Moreau, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076609 · Cited by 12 · see citing works
The Impact of Metal and Heavy Metal Concentrations on Vancomycin Resistance in Staphylococcus aureus within Milk Produced by Cattle Farms and the Health Risk Assessment in Kurdistan Province, Iran
Sadeghian, Y., Raeeszadeh, M., & Darehabi, H. K. (2024) · Animals · doi:10.3390/ani14010148 · Cited by 12 · see citing works
Zinc acquisition and its contribution to Klebsiella pneumoniae virulence
Maunders, E. A., Giles, M. W., Ganio, K., Cunningham, B. A., Bennett-Wood, V. R., Cole, G. B., Ng, D., Lai, C. C.-L., Neville, S. L., Moraes, T. F., et al. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1322973 · Cited by 12 · see citing works
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Investigation of Zur-regulated metal transport systems reveals an unexpected role of pyochelin in zinc homeostasis
(2024) · doi:10.1128/mbio.02395-24 · Cited by 12 · see citing works
Pyrazolopyrimidinones, a novel class of copper-dependent bactericidal antibiotics against multi-drug resistant S. aureus
Crawford, C. L., Dalecki, A. G., Narmore, W. T., Hoff, J. S., Hargett, A. A., Renfrow, M. B., Zhang, M., Kalubowilage, M., Bossmann, S. H., Queern, S. L., et al. (2019) · Metallomics · doi:10.1039/c8mt00316e · Cited by 12 · see citing works
Disruption of Phosphate Homeostasis Sensitizes Staphylococcus aureus to Nutritional Immunity
Kelliher, J. L., Brazel, E. B., Radin, J. N., Joya, E. S., Solórzano, P. K. P., Neville, S. L., McDevitt, C. A., & Kehl‐Fie, T. E. (2020) · Infection and Immunity · doi:10.1128/iai.00102-20 · Cited by 12 · see citing works
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Determinants of bacterial survival and proliferation in blood
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Luo, Z., Luo, S., Ju, Y., Ding, P., Xu, J., Gu, Q., & Zhou, H. (2021) · The FASEB Journal · doi:10.1096/fj.202002287rr · Cited by 11 · see citing works
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Peng, E. D., & Schmitt, M. P. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221711 · Cited by 11 · see citing works
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Peng, M., Xu, Y., Dou, B., Yang, F., He, Q., Liu, Z., Gao, T., Liu, W., Yang, K., Guo, R., et al. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.04337-22 · Cited by 9 · see citing works
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Neff, S. L., Doing, G., Reiter, T. E., Hampton, T. H., Greene, C. S., & Hogan, D. A. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.03157-23 · Cited by 9 · see citing works
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Maurakis, S. A., & Cornelissen, C. N. (2020) · Journal of Visualized Experiments · doi:10.3791/60903 · Cited by 9 · see citing works
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Elhakim, Y. A., Ali, A. E., Hosny, A. E.-D. M. S., & Abdeltawab, N. F. (2021) · Pathogens · doi:10.3390/pathogens10101228 · Cited by 9 · see citing works
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Teoh, W. P., Resko, Z. J., Flury, S., & Alonzo, F. (2019) · Journal of Bacteriology · doi:10.1128/jb.00446-19 · Cited by 8 · see citing works
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McFarlane, J. S., & Lamb, A. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14800-0 · Cited by 8 · see citing works
Potential next generation targets for antibacterial agent's discovery and development
Gupta, P., Yadav, P., Lata, M., Chaudhary, S., Telang, V., Kishore, R., Kishan, J., Goswami, K., Arockiaraj, J., Singh, L. R., et al. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118188 · Cited by 8 · see citing works
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Cho, H., Masters, T. L., Greenwood‐Quaintance, K. E., Johnson, S. P., Jeraldo, P., Chia, N., Pu, M., Abdel, M. P., & Patel, R. (2021) · MicrobiologyOpen · doi:10.1002/mbo3.1256 · Cited by 7 · see citing works
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Secli, V., Biagio, C. D., Martini, A., Michetti, E., Pacello, F., Ammendola, S., & Battistoni, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24020944 · Cited by 7 · see citing works
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Shull, L. M., Wolter, D. J., Kunkle, D. E., Legg, K. A., Giedroc, D. P., Skaar, E. P., Hoffman, L. R., & Reniere, M. L. (2025) · mBio · doi:10.1128/mbio.00374-25 · Cited by 6 · see citing works
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Gan, Y., Zhang, J., Qi, F., Grice, E. A., Garza, L. A., & Wang, G. (2025) · Med · doi:10.1016/j.medj.2025.100847 · Cited by 5 · see citing works
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Mujchariyakul, W., Walsh, C. J., Giulieri, S. G., Cramond, C., Cao, K. L., Stinear, T. P., Howden, B. P., Guérillot, R., & Hachani, A. (2026) · mSystems · doi:10.1128/msystems.01183-25 · Cited by 5 · see citing works
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Peet, J. J. Y., Phan, A. D., Oglesby, A. G., & Nolan, E. M. (2024) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.3c00539 · Cited by 5 · see citing works
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Wang, J., Capdevila, D. A., & Giedroc, D. P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14675-x · Cited by 5 · see citing works
Interplay between Supramolecular and Coordination Interactions in Synthetic Amphiphiles: Triggering Metal Starvation and Anchorage onto MRSA Cell Surface
Dey, P., Das, G. C., & Ramesh, A. (2020) · Langmuir · doi:10.1021/acs.langmuir.9b03073 · Cited by 5 · see citing works
Microgeography of staphyloccoci in human tissue explains antibiotic failurePreprint
Tripathi, V., Morin, B., Antelo-Varela, M., Loriol, A. A., Kurg, K., Jakonia, S., Ehsan, A., Herbert, S., Ferrand, A., Sauteur, L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.12.675782 · Cited by 7 · see citing works

Elucidating the mechanisms by which the human pathogen staphylococcus aureus resists host-imposed zinc starvation
Grim, K. P. (2020) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Self-citation
Host subversion of bacterial metallophore usage drives copper intoxication
Hossain, S., Morey, J. R., Neville, S. L., Ganio, K., Radin, J. N., Norambuena, J., Boyd, J. M., McDevitt, C. A., & Kehl‐Fie, T. E. (2023) · mBio · doi:10.1128/mbio.01350-23 · Cited by 16 · see citing works
Self-citation
MntABC and MntH Contribute to Systemic Staphylococcus aureus Infection by Competing with Calprotectin for Nutrient Manganese
Kehl-Fie, T. E., Zhang, Y., Moore, J. L., Farrand, A. J., Hood, M. I., Rathi, S., Chazin, W. J., Caprioli, R. M., & Skaar, E. P. (2013) · Infection and Immunity · doi:10.1128/iai.00420-13 · Cited by 213 · see citing works
Self-citation
Elucidating the metabolic and signaling pathways that enable Staphylococcus aureus to overcome host-imposed nutrient starvation
Kim, P. (2017) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Self-citation
Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity
Grim, K. P., Radin, J. N., Solórzano, P. K. P., Morey, J. R., Frye, K. A., Ganio, K., Neville, S. L., McDevitt, C. A., & Kehl‐Fie, T. E. (2020) · Journal of Bacteriology · doi:10.1128/jb.00014-20 · Cited by 22 · see citing works
Self-citation

Authors: Grim, K. P., San Francisco, B., Radin, J. N., Brazel, E. B., Kelliher, J. L., Párraga Solórzano, P. K., Kim, P. C., McDevitt, C. A., & Kehl-Fie, T. E.
Affiliations: University of Illinois Urbana-Champaign (US)
Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, Illinois, USA
The University of Adelaide (AU)
Department of Microbiology, University of Illinois Urbana-Champaign, Urbana, Illinois, USA
ORCID: Radin, Jana N.
Brazel, Erin B.
Kelliher, Jessica L.
McDevitt, Christopher A.
Venue: mBio
Publisher: American Society for Microbiology
Published: 2017-11-08
Volume: 8
Issue: 5
ISSN: 2150-7511 (ISSN-L)
2161-2129
DOI: 10.1128/mbio.01281-17
PMC: PMC5666155
OpenAlex: W2767136855
Cited by: 152
References: 77
Citations by year: 2026: 19 · 2025: 18 · 2024: 17 · 2023: 13 · 2022: 15 · 2021: 22 · 2020: 18 · 2019: 21 · 2018: 9
FWCI: 8.89
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
journals.asm.org/non-commercial-tdm-license (tdm)
Locations: mBio (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Repositorio Institucional de la Universidad de las Fuerzas Armadas ESPE (Universidad de las Fuerzas Armadas ESPE) (submittedVersion, other-oa)
Greater South Information System
Funders: Institute for Genomic Biology Post Doctoral Fellowship
HHS | National Institutes of Health (K22 AI104805, R01 AI118880)
Department of Health | National Health and Medical Research Council (1080784, 1122582)
Australian Research Council (DP150104515, DP170102102)
March of Dimes Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: Staphylococcus aureus, metallophores, zinc uptake, nutritional immunity, calprotectin, zinc starvation, bacterial virulence
MeSH terms: Bacterial Proteins, Imidazoles, Staphylococcal Infections, Staphylococcus aureus, Zinc, Gene Expression Regulation, Bacterial, Siderophores, Membrane Transport Proteins, Leukocyte L1 Antigen Complex, Host-Pathogen Interactions

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

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