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Metal ion homeostasis is vital to the survival of this pathogen across diverse biological sites and contributes significantly to colonization and invasive disease. Microarray and qRT-PCR analysis revealed an upregulation of an uncharacterized operon (SP1433-1438) in pneumococci subjected to metal-chelation by N,N,N\u2032,N\u2032-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN). Supplementation of zinc, cobalt, and nickel following TPEN treatment significantly abrogated induction. BLASTP comparisons and protein topology analysis predicted this locus to encode components of ATP binding cassette (ABC) transporters involved in multidrug resistance (SP1434-1435) and energy-coupling factor (ECF) transporters (SP1436-1438). Inductively coupled plasma mass spectrometry (ICP-MS) analysis identified differences in intracellular metal content in a \u03941434-8 mutant strain compared to parental T4R. Further, analysis of the secreted metabolome of WT and \u03941434-8 strains identified significant changes in pneumococcal glycolytic and amino acid metabolic pathways, indicating a shift towards mixed acid fermentation. Additionally, proteomic analysis revealed differentially expressed proteins in the \u03941434-8 mutant strain, with nearly 20% regulated by the global catabolite repressor, CcpA. Based on these findings, we propose that the transporters encoded by SP1433-1438 are involved in regulating the central metabolism of S. pneumoniae and contributing to bacterial survival during metal stress.<\/jats:p>","DOI":"10.1039\/d0mt00118j","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T08:43:44Z","timestamp":1594975424000},"page":"1416-1427","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>Streptococcus pneumoniae<\/i> metal homeostasis alters cellular metabolism"],"prefix":"10.1093","volume":"12","author":[{"given":"Lindsey R","family":"Burcham","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca A","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel C","family":"Caulkins","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph P","family":"Emerson","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bindu","family":"Nanduri","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason W","family":"Rosch","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas C","family":"Fitzkee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-796X","authenticated-orcid":false,"given":"Justin A","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"2021121004462864400_cit1","volume-title":"Epidemiology and Prevention of Vaccine-Preventable Diseases","author":"Hamborsky","year":"2015"},{"key":"2021121004462864400_cit2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00401-015-1531-z","article-title":"Host\u2013pathogen interactions in bacterial meningitis","volume":"131","author":"Doran","year":"2016","journal-title":"Acta Neuropathol."},{"key":"2021121004462864400_cit3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1085\/jgp.201411164","article-title":"Structural diversity of ABC transporters","volume":"143","author":"Ter Beek","year":"2014","journal-title":"J. Gen. Physiol."},{"key":"2021121004462864400_cit4","doi-asserted-by":"crossref","first-page":"16301","DOI":"10.1021\/bi0513103","article-title":"In Vitro functional characterization of BtuCD-F, the Escherichia coli ABC transporter for vitamin B12 uptake","volume":"44","author":"Borths","year":"2005","journal-title":"Biochemistry"},{"key":"2021121004462864400_cit5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0923-2508(01)01200-1","article-title":"ABC transporter-mediated uptake of iron, siderophores, heme and vitamin B12","volume":"152","author":"Koster","year":"2001","journal-title":"Res. Microbiol."},{"key":"2021121004462864400_cit6","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0923-2508(01)01195-0","article-title":"A new family of high-affinity ABC manganese and zinc permeases","volume":"152","author":"Claverys","year":"2001","journal-title":"Res. 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Biol."},{"key":"2021121004462864400_cit12","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nature08300","article-title":"Metalloproteins and metal sensing","volume":"460","author":"Waldron","year":"2009","journal-title":"Nature"},{"key":"2021121004462864400_cit13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jama.1975.03240130021018","article-title":"Nutritional immunity. Host\u2019s attempt to withold iron from microbial invaders","volume":"231","author":"Weinberg","year":"1975","journal-title":"JAMA, J. Am. Med. 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Microbiol."},{"key":"2021121004462864400_cit17","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/j.1365-2958.2011.07862.x","article-title":"Zinc uptake by Streptococcus pneumonia depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence","volume":"82","author":"Bayle","year":"2011","journal-title":"Mol. Microbiol."},{"key":"2021121004462864400_cit18","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fcimb.2015.00091","article-title":"The regulation of the AdcR regulon in Streptococcus pneumoniae depends both on Zn(2+)- and Ni(2+)-Availability","volume":"5","author":"Manzoor","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"2021121004462864400_cit19","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1086\/380564","article-title":"Capsular Expression in Streptococcus pneumoniae Negatively Affects Spontaneous and Antibiotic-Induced Lysis and Contributes to Antibiotic Tolerance","volume":"189","author":"Fernebro","year":"2004","journal-title":"J. Infect. Dis."},{"key":"2021121004462864400_cit20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF02789105","article-title":"PCR-mediated recombination and mutagenesis","volume":"3","author":"Horton","year":"1995","journal-title":"Mol. Biotechnol."},{"key":"2021121004462864400_cit21","doi-asserted-by":"crossref","first-page":"6990","DOI":"10.1002\/anie.201404111","article-title":"Ultrahigh-Resolution NMR Spectroscopy","volume":"53","author":"Foroozandeh","year":"2014","journal-title":"Angew. Chem., Int. Ed."},{"key":"2021121004462864400_cit22","doi-asserted-by":"crossref","first-page":"15410","DOI":"10.1039\/C5CC06293D","article-title":"Measuring couplings in crowded NMR spectra: pure shift NMR with multiplet analysis","volume":"51","author":"Foroozandeh","year":"2015","journal-title":"Chem. Commun."},{"key":"2021121004462864400_cit23","doi-asserted-by":"crossref","first-page":"3938","DOI":"10.1002\/anie.200351947","article-title":"Elimination of Zero- Quantum Interference in Two-Dimensional NMR Spectra","volume":"42","author":"Thrippleton","year":"2003","journal-title":"Angew. Chem., Int. Ed."},{"key":"2021121004462864400_cit24","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/BF00197809","article-title":"NMRPipe: A multidimensional spectral processing system based on UNIX pipes","volume":"6","author":"Delaglio","year":"1995","journal-title":"J. Biomol. 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Rep."},{"key":"2021121004462864400_cit29","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1002\/1615-9861(200209)2:9<1156::AID-PROT1156>3.0.CO;2-4","article-title":"Proteomic characterization of wheat amyloplasts using identification of proteins by tandem mass spectrometry","volume":"2","author":"Andon","year":"2002","journal-title":"Proteomics"},{"key":"2021121004462864400_cit30","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/pmic.200400942","article-title":"Comparative proteome analyses of human plasma following in vivo lipopolysaccharide administration using multidimensional separations coupled with tandem mass spectrometry","volume":"5","author":"Qian","year":"2005","journal-title":"Proteomics"},{"key":"2021121004462864400_cit31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang da","year":"2009","journal-title":"Nat. Protoc."},{"key":"2021121004462864400_cit32","doi-asserted-by":"crossref","first-page":"16289","DOI":"10.1074\/jbc.M011059200","article-title":"Polyamine enhancement of the synthesis of adenylate cyclase at the translational level and the consequential stimulation of the synthesis of the RNA polymerase B28 subunit","volume":"276","author":"Yoshida","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021121004462864400_cit33","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: quality-controlled protein\u2013protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021121004462864400_cit34","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gkv1145","article-title":"2016 update of the PRIDE database and its related tools","volume":"44","author":"Vizcaino","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2021121004462864400_cit35","doi-asserted-by":"crossref","first-page":"D459","DOI":"10.1093\/nar\/gkn757","article-title":"DOOR: a database for prokaryotic operons","volume":"37","author":"Mao","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2021121004462864400_cit36","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1101\/gr.3844805","article-title":"The MicrobesOnline Web site for comparative genomics","volume":"15","author":"Alm","year":"2005","journal-title":"Genome Res."},{"key":"2021121004462864400_cit37","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1128\/AAC.01298-12","article-title":"Functional Analysis of Pneumococcal Drug Efflux Pumps Associates the MATE DinF Transporter with Quinolone Susceptibility","volume":"57","author":"Tocci","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021121004462864400_cit38","first-page":"460","article-title":"Depletion of Intracellular Zinc and Copper with TPEN Results in Apoptosis of Cultured Human Retinal Pigment Epithelial Cells","volume":"42","author":"Hyun","year":"2001","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"2021121004462864400_cit39","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1165\/rcmb.2008-0409OC","article-title":"Nickel mobilizes intracellular zinc to induce metallothionein in human airway epithelial cells","volume":"41","author":"Nemec","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021121004462864400_cit40","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1016\/S0021-9258(18)89421-2","article-title":"Cytosolic Ca2+ homeostasis in ehrlich and yoshida carcinomas. A new, membrane-permeant chelator of heavy metals reveals that these ascites tumor cell lines have normal cytosolic free Ca2+","volume":"260","author":"Arslan","year":"1985","journal-title":"J. Biol. Chem."},{"key":"2021121004462864400_cit41","doi-asserted-by":"crossref","first-page":"10799","DOI":"10.1038\/srep10799","article-title":"Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes","volume":"5","author":"Ong","year":"2015","journal-title":"Sci. Rep."},{"key":"2021121004462864400_cit42","doi-asserted-by":"crossref","first-page":"D111","DOI":"10.1093\/nar\/gkp894","article-title":"RegPrecise: a database of curated genomic inferences of transcriptional regulatory interactions in prokaryotes","volume":"38","author":"Novichkov","year":"2010","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"2021121004462864400_cit43","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: a hub for protein information","volume":"43","author":"Uniprot Consortium","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2021121004462864400_cit44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/0470857897.ch8","article-title":"The KEGG database, silico simulation of biological processes","volume":"247","author":"Kanehisa","year":"2002","journal-title":"Novartis Found. Symp."},{"key":"2021121004462864400_cit45","doi-asserted-by":"crossref","first-page":"8340","DOI":"10.1128\/JB.187.24.8340-8349.2005","article-title":"Catabolite control protein A (CcpA) contributes to virulence and regulation of sugar metabolism in Streptococcus pneumoniae","volume":"187","author":"Iyer","year":"2005","journal-title":"J. Bacteriol."},{"key":"2021121004462864400_cit46","doi-asserted-by":"crossref","first-page":"e26707","DOI":"10.1371\/journal.pone.0026707","article-title":"CcpA Ensures Optimal Metabolic Fitness of Streptococcus pneumoniae","volume":"6","author":"Carvalho","year":"2011","journal-title":"PLoS One"},{"key":"2021121004462864400_cit47","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/j.1365-2958.2010.07339.x","article-title":"The global nutritional regulator CodY is an essential protein in the human pathogen Streptococcus pneumoniae","volume":"78","author":"Caymaris","year":"2010","journal-title":"Mol. Microbiol."},{"key":"2021121004462864400_cit48","doi-asserted-by":"crossref","first-page":"44594","DOI":"10.1074\/jbc.M111.295832","article-title":"Regulation of arginine acquisition and virulence gene expression in the human pathogen Streptococcus pneumoniae by transcription regulators ArgR1 and AhrC","volume":"286","author":"Kloosterman","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2021121004462864400_cit49","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1574-6968.2011.02293.x","article-title":"Transcriptional repressor Rex is involved in regulation of oxidative stress response and biofilm formation by Streptococcus mutans","volume":"320","author":"Bitoun","year":"2011","journal-title":"FEMS Microbiol. Lett."},{"key":"2021121004462864400_cit50","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.1128\/JB.00074-06","article-title":"Global Regulatory Impact of ClpP Protease of Staphylococcus aureus on Regulons Involved in Virulence, Oxidative Stress Response, Autolysis, and DNA Repair","volume":"188","author":"Michel","year":"2006","journal-title":"J. Bacteriol."},{"key":"2021121004462864400_cit51","doi-asserted-by":"crossref","first-page":"7295","DOI":"10.1128\/JB.183.24.7295-7307.2001","article-title":"Regulation of Streptococcus pneumoniae clp Genes and Their Role in Competence Development and Stress Survival","volume":"183","author":"Chastanet","year":"2001","journal-title":"J. Bacteriol."},{"key":"2021121004462864400_cit52","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1039\/c1mt00030f","article-title":"Transcriptional response of Streptococcus pneumoniae to Zn2+ limitation and the repressor\/activator function of AdcR","volume":"3","author":"Shafeeq","year":"2011","journal-title":"Metallomics"},{"key":"2021121004462864400_cit53","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00165-18","article-title":"Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08","volume":"3","author":"G\u00f3mez-Mejia","year":"2018","journal-title":"mSphere"},{"key":"2021121004462864400_cit54","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1128\/JB.01170-06","article-title":"The Two-Component Regulatory System TCS08 Is Involved in Cellobiose Metabolism of Streptococcus pneumoniae R6","volume":"189","author":"McKessar","year":"2007","journal-title":"J. Bacteriol."},{"key":"2021121004462864400_cit55","doi-asserted-by":"crossref","first-page":"e1005026","DOI":"10.1371\/journal.ppat.1005026","article-title":"Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections","volume":"11","author":"Cho","year":"2015","journal-title":"PLoS Pathog."},{"key":"2021121004462864400_cit56","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0891-5849(93)90168-T","article-title":"The centennial of the Fenton reaction","volume":"15","author":"Koppenol","year":"1993","journal-title":"Free Radicals Biol. Med."},{"key":"2021121004462864400_cit57","doi-asserted-by":"crossref","first-page":"1447s","DOI":"10.1093\/jn\/130.5.1447S","article-title":"The antioxidant properties of zinc","volume":"130","author":"Powell","year":"2000","journal-title":"J. Nutr."},{"key":"2021121004462864400_cit58","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1128\/IAI.68.5.2819-2826.2000","article-title":"Role of manganese-containing superoxide dismutase in oxidative stress and virulence of Streptococcus pneumoniae","volume":"68","author":"Yesilkaya","year":"2000","journal-title":"Infect. Immun."},{"key":"2021121004462864400_cit59","doi-asserted-by":"crossref","first-page":"4260","DOI":"10.1074\/jbc.M111.304311","article-title":"Characterization of central carbonmetabolism of Streptococcus pneumoniae by isotopologue profiling","volume":"287","author":"Hartel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2021121004462864400_cit60","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3390\/biom4020419","article-title":"Zinc-binding cysteines: diverse functions and structural motifs","volume":"4","author":"Pace","year":"2014","journal-title":"Biomolecules"},{"key":"2021121004462864400_cit61","doi-asserted-by":"crossref","first-page":"e33320","DOI":"10.1371\/journal.pone.0033320","article-title":"A Functional Genomics Approach to Establish the Complement of Carbohydrate Transporters in Streptococcus pneumoniae","volume":"7","author":"Bidossi","year":"2012","journal-title":"PLoS One"},{"key":"2021121004462864400_cit62","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1128\/AEM.00499-15","article-title":"Sialic Acid-Mediated Gene Expression in Streptococcus pneumoniae and Role of NanR as a Transcriptional Activator of the nan Gene Cluster","volume":"81","author":"Afzal","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"2021121004462864400_cit63","doi-asserted-by":"crossref","first-page":"43587","DOI":"10.1038\/srep43587","article-title":"Pneumococcal galactose catabolism is controlled by multiple regulators acting on pyruvate formate lyase","volume":"7","author":"Al-Bayati","year":"2017","journal-title":"Sci. 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