BioPAX pathway converted from "Ion influx/efflux at host-pathogen interface" in the Reactome database. Ion influx/efflux at host-pathogen interface This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> LEFT-TO-RIGHT NRAMP1 transports divalent metal ions across phagosomal membranes of macrophages This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> H+ proton hydron Reactome DB_ID: 70106 cytosol GENE ONTOLOGY GO:0005829 hydron [ChEBI:15378] hydron ChEBI CHEBI:15378 Reactome Database ID Release 78 70106 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70106 Reactome R-ALL-70106 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-70106.4 Reactome http://www.reactome.org COMPOUND C00080 additional information MI MI:0361 2 Converted from EntitySet in Reactome Divalent metals transported by NRAMP1 Reactome DB_ID: 445829 Zn2+ Zn++ zinc(2+) Zinc ion Zn(II) Reactome DB_ID: 29426 zinc(2+) [ChEBI:29105] zinc(2+) ChEBI CHEBI:29105 Reactome Database ID Release 78 29426 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29426 Reactome R-ALL-29426 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29426.3 COMPOUND C00038 Fe2+ iron (ferrous) iron atom Fe(II) Fe++ Iron Fe3+ Fe(III) Reactome DB_ID: 71067 iron(2+) [ChEBI:29033] iron(2+) FE (II) ION Fe2+ Fe(2+) iron ion(2+) Fe(II) Ferrous ion ChEBI CHEBI:29033 Reactome Database ID Release 78 71067 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71067 Reactome R-ALL-71067 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-71067.4 COMPOUND C00023 Mn2+ Manganese manganese(2+) Mn(II) Reactome DB_ID: 29418 manganese(2+) [ChEBI:29035] manganese(2+) Mn(2+) MANGANESE (II) ION manganese, ion (Mn2+) manganese(II) manganous ion ChEBI CHEBI:29035 Reactome Database ID Release 78 29418 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29418 Reactome R-ALL-29418 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29418.3 COMPOUND C00034 Reactome Database ID Release 78 445829 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=445829 Reactome R-ALL-445829 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-445829.1 H+ hydron Reactome DB_ID: 1470067 phagocytic vesicle lumen GENE ONTOLOGY GO:0097013 Reactome Database ID Release 78 1470067 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1470067 Reactome R-ALL-1470067 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1470067.3 2 Converted from EntitySet in Reactome Divalent metals transported by NRAMP1 Reactome DB_ID: 445832 Mn2+ Manganese manganese(2+) Mn(II) Reactome DB_ID: 1562549 Reactome Database ID Release 78 1562549 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1562549 Reactome R-ALL-1562549 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1562549.3 Zn2+ zinc(2+) Reactome DB_ID: 1562550 Reactome Database ID Release 78 1562550 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1562550 Reactome R-ALL-1562550 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1562550.3 Fe2+ Reactome DB_ID: 1222286 Reactome Database ID Release 78 1222286 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1222286 Reactome R-ALL-1222286 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1222286.4 Reactome Database ID Release 78 445832 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=445832 Reactome R-ALL-445832 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-445832.1 ACTIVATION P41251 Slc11a1 SLC11A1 Reactome DB_ID: 9783939 late endosome membrane GENE ONTOLOGY GO:0031902 UniProt:P41251 Slc11a1 Mus musculus NCBI Taxonomy 10090 UniProt P41251 1 EQUAL 550 EQUAL Reactome Database ID Release 78 9783939 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9783939 Reactome R-MMU-437103 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-437103.1 GENE ONTOLOGY GO:0051139 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 78 9783940 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9783940 Reactome Database ID Release 78 9783942 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9783942 Reactome R-MMU-435171 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-435171.1 Natural resistance-associated macrophage proteins (NRAMPs) regulate macrophage activation for antimicrobial activity against intracellular pathogens. They do this by mediating bivalent metal ion transport across macrophage membranes and the subsequent use of these ions in the Fenton/and or Haber–Weiss reactions of free radical formation.<br>The human gene SLC11A1 encodes NRAMP1 (Kishi F, 2004; Kishi F and Nobumoto M, 1995) which can utilize the protonmotive force to mediate divalent iron (Fe2+), zinc (Zn2+) and manganese (Mn2+) influx to or efflux from phagosomes. 7980580 Pubmed 1994 Isolation and characterization of human Nramp cDNA Kishi, F Biochem Biophys Res Commun 204:1074-80 8537108 Pubmed 1995 Identification of natural resistance-associated macrophage protein in peripheral blood lymphocytes Kishi, F Nobumoto, M Immunol Lett 47:93-6 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT 7.2.2.9 ATP7A transports cytosolic Cu2+ to phagosomal lumen Copper export from cells by copper-transporting ATPase1 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 78 113592 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592 Reactome R-ALL-113592 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.5 COMPOUND C00002 H2O water Reactome DB_ID: 29356 water [ChEBI:15377] water ChEBI CHEBI:15377 Reactome Database ID Release 78 29356 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356 Reactome R-ALL-29356 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.5 COMPOUND C00001 Atox1:Cu1+ Reactome DB_ID: 3697902 Atox1 Copper transport protein ATOX1 ATOX1_MOUSE Reactome DB_ID: 3697844 UniProt:O08997 Atox1 Atox1 FUNCTION Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense (By similarity).SUBUNIT Interacts with ATP7B (By similarity). Interacts with ATP7A (By similarity).DOMAIN The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion via the cysteine residues within the CXXC motif. The transfer of Cu(+) ion from ATOX1 to ATP7A involves the formation of a three-coordinate Cu(+)-bridged heterodimer where the metal is shared between the two metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch between two coordination modes, forming two links with one protein and one with the other. Cisplatin, a chemotherapeutic drug, can bind the CXXC motif and hinder the release of Cu(+) ion.SIMILARITY Belongs to the ATX1 family. UniProt O08997 1 EQUAL 68 EQUAL Reactome Database ID Release 78 3697844 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3697844 Reactome R-MMU-3697844 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-3697844.1 1 Cu1+ Cu(I) copper(1+) Reactome DB_ID: 3299744 copper(1+) [ChEBI:49552] copper(1+) COPPER (I) ION Cu(+) copper(1+) ion copper cation copper(I) cation cuprous ion ChEBI CHEBI:49552 Reactome Database ID Release 78 3299744 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3299744 Reactome R-ALL-3299744 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-3299744.3 1 Reactome Database ID Release 78 3697902 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3697902 Reactome R-MMU-3697902 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-3697902.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 29370 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 78 29370 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370 Reactome R-ALL-29370 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.5 COMPOUND C00008 Cu1+ Copper copper(1+) Reactome DB_ID: 6803540 Reactome Database ID Release 78 6803540 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6803540 Reactome R-ALL-6803540 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-6803540.3 COMPOUND C00070 Pi Orthophosphate hydrogenphosphate Phosphate Inorganic Phosphate Reactome DB_ID: 29372 hydrogenphosphate [ChEBI:43474] hydrogenphosphate hydrogen phosphate phosphate [PO3(OH)](2-) INORGANIC PHOSPHATE GROUP HYDROGENPHOSPHATE ION HPO4(2-) [P(OH)O3](2-) ChEBI CHEBI:43474 Reactome Database ID Release 78 29372 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29372 Reactome R-ALL-29372 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29372.4 COMPOUND C00009 ACTIVATION ATP7A:PDZD11 Reactome DB_ID: 9839274 phagocytic vesicle membrane GENE ONTOLOGY GO:0030670 Atp7a ATP7A Q64430 Reactome DB_ID: 9839272 UniProt:Q64430 Atp7a UniProt Q64430 1 EQUAL 1500 EQUAL Reactome Database ID Release 78 9839272 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9839272 Reactome R-MMU-6803546 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-6803546.1 1 Pdzd11 PDZD11 Q9CZG9 Reactome DB_ID: 9769897 UniProt:Q9CZG9 Pdzd11 UniProt Q9CZG9 1 EQUAL 140 EQUAL Reactome Database ID Release 78 9769897 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9769897 Reactome R-MMU-5358989 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5358989.1 1 Reactome Database ID Release 78 9839274 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9839274 Reactome R-MMU-6803541 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-6803541.1 GENE ONTOLOGY GO:0043682 Reactome Database ID Release 78 9839275 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9839275 Reactome Database ID Release 78 9839277 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9839277 Reactome R-MMU-6803545 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-6803545.1 Copper is an essential cofactor of key metabolic enzymes (Linder MC & Hazegh-Azam M 1996). Under normal conditions, the biosynthetic incorporation of copper into secreted and plasma membrane-bound proteins requires activity of the copper-transporting P1B-type ATPases (Cu-ATPases), ATP7A and ATP7B (Camakaris J et al. 1999; La Fontaine S & Mercer JF 2007; Lutsenko S et al. 2007). The Cu-ATPases also export excess copper from the cell and thus critically contribute to the homeostatic control of copper (Camakaris J et al. 1999; La Fontaine S & Mercer JF 2007). However, during bacterial infection phagocytic cells accumulate copper Cu(I) in cytoplasmic vesicles that partially fuse with the phagolysosome, attacking invading microbes with toxic levels of Cu (Festa RA & Thiele DJ 2012). The accumulation of Cu(I) in the phagosome may be dependent upon the trafficking of ATP7A to the membranes of these vesicles (Fu Y et al. 2014). Silencing of ATP7A expression in mouse RAW264.7 macrophages attenuated bacterial killing, suggesting a role for ATP7A-dependent copper transport in the bactericidal activity of macrophages (White C et al. 2009). Copper toxicity targets iron-sulfur containing proteins via iron displacement from solvent-exposed iron-sulfur clusters (Macomber L & Imlay JA 2009; Chillappagari S et al. 2010; Djoko KY & McEwan AG 2013). Copper resistance has been shown to be required for virulence in two animal models of mycobacterial infection (Wolschendorf F et al. 2011; Shi X et al. 2014).<p>Mutations in the gene encoding ATP7A results in a severe copper-deficiency known as Menkes disease (Kaler SG 2011). 20233928 Pubmed 2010 Copper stress affects iron homeostasis by destabilizing iron-sulfur cluster formation in Bacillus subtilis Chillappagari, Shashi Seubert, Andreas Trip, Hein Kuipers, Oscar P Marahiel, Mohamed A Miethke, Marcus J. Bacteriol. 192:2512-24 25310275 Pubmed 2014 Copper transport and trafficking at the host-bacterial pathogen interface Fu, Yue Chang, Feng-Ming James Giedroc, David P Acc. Chem. Res. 47:3605-13 17562324 Pubmed 2007 Biochemical basis of regulation of human copper-transporting ATPases Lutsenko, Svetlana LeShane, Erik S Shinde, Ujwal Arch. Biochem. Biophys. 463:134-48 8615367 Pubmed 1996 Copper biochemistry and molecular biology Linder, M C Hazegh-Azam, M Am. J. Clin. Nutr. 63:797S-811S 24549843 Pubmed 2014 The copper-responsive RicR regulon contributes to Mycobacterium tuberculosis virulence Shi, Xiaoshan Festa, Richard A Ioerger, Thomas R Butler-Wu, Susan Sacchettini, James C Darwin, K Heran Samanovic, Marie I MBio 5: 17531189 Pubmed 2007 Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis La Fontaine, Sharon Mercer, Julian F B Arch. Biochem. Biophys. 463:149-67 19808669 Pubmed 2009 A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity White, Carine Lee, Jaekwon Kambe, Taiho Fritsche, Kevin Petris, Michael J J. Biol. Chem. 284:33949-56 23895035 Pubmed 2013 Antimicrobial action of copper is amplified via inhibition of heme biosynthesis Djoko, Karrera Y McEwan, Alastair G ACS Chem. Biol. 8:2217-23 26055706 Pubmed 2015 The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens Djoko, Karrera Y Ong, Cheryl-lynn Y Walker, Mark J McEwan, Alastair G J. Biol. Chem. 290:18954-61 21205886 Pubmed 2011 Copper resistance is essential for virulence of Mycobacterium tuberculosis Wolschendorf, Frank Ackart, David Shrestha, Tej B Hascall-Dove, Laurel Nolan, Scott Lamichhane, Gyanu Wang, Ying Bossmann, Stefan H Basaraba, Randall J Niederweis, Michael Proc. Natl. Acad. Sci. U.S.A. 108:1621-6 19416816 Pubmed 2009 The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity Macomber, Lee Imlay, James A Proc. Natl. Acad. Sci. U.S.A. 106:8344-9 23028306 Pubmed 2012 Copper at the front line of the host-pathogen battle Festa, Richard A Thiele, Dennis J PLoS Pathog. 8:e1002887 22389498 Pubmed 2012 Copper homeostasis at the host-pathogen interface Hodgkinson, Victoria Petris, Michael J J. Biol. Chem. 287:13549-55 21221114 Pubmed 2011 ATP7A-related copper transport diseases-emerging concepts and future trends Kaler, Stephen G Nat Rev Neurol 7:15-29 10425169 Pubmed 1999 Molecular mechanisms of copper homeostasis Camakaris, J Voskoboinik, I Mercer, J F Biochem. Biophys. Res. Commun. 261:225-32 Reactome Database ID Release 78 9861816 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9861816 Reactome R-MMU-6803544 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-6803544.1 Essential metal ions act as co-factors that enable enzymes to catalyse a wider range of chemical transformations than would be achievable using solely organic catalysts. The precise metal requirements of organisms vary between species, environmental niches, metabolic states and circadian rhythms. <br>Metals are required cofactors for numerous processes that are essential to both pathogen and host. They are coordinated in enzymes responsible for DNA replication and transcription, relief from oxidative stress, and cellular respiration. However, excess transition metals can be toxic due to their ability to cause spontaneous redox cycling and disrupt normal metabolic processes. Vertebrates have evolved intricate mechanisms to limit the availability of some crucial metals while concurrently flooding sites of infection with antimicrobial concentrations of other metals. <br> Both pathogens and hosts have complex regulatory systems for metal homeostasis. Understanding these provides strategies for fighting pathogens, either by excluding essential metals from the microbes, by delivery of excess metals to cause toxicity, or by complexing metals in microorganisms. 25211180 Pubmed 2014 Metal limitation and toxicity at the interface between host and pathogen Becker, Kyle W Skaar, Eric P FEMS Microbiol. Rev. 38:1235-49 26055725 Pubmed 2015 Introduction: Metals in Biology: METALS AT THE HOST-PATHOGEN INTERFACE Guengerich, FP J. Biol. Chem. 290:18943-4 2468370 Pubmed 1988 Some examples of the functions of metal ions in biology Williams, R J Biosci. Rep. 8:653-68 22138493 Pubmed 2012 Metals in biology: defining metalloproteomes Yannone, Steven M Hartung, Sophia Menon, Angeli L Adams, Michael W W Tainer, JA Curr. Opin. Biotechnol. 23:89-95 192123 Pubmed 1977 The role of metals in enzyme activity Riordan, J F Ann. Clin. Lab. Sci. 7:119-29