The iron hand of uropathogenic Escherichia coli: the role of transition metal control in virulence

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1 Gupta K, Grigoryan L, Trautner B. Urinary tract infection. Ann. Intern. Med. 167(7), ITC49–ITC64 (2017).
  MedlineGoogle Scholar
• 2 Stamey TA. Recurrent urinary tract infections in female patients: an overview of management and treatment [with panel discussion]. Rev. Infect. Dis. 9, S195–S210 (1987).
  MedlineGoogle Scholar
• 3 Mysorekar IU, Hultgren SJ. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc. Natl Acad. Sci. USA 103(38), 14170–14175 (2006).
  Medline CASGoogle Scholar
• 4 Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ. Detection of intracellular bacterial communities in human urinary tract infection. PLoS Med. 4(12), e329 (2007).
  MedlineGoogle Scholar
• 5 Caspi R, Altman T, Dreher K et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res. 40, D742–D753 (2012).
  Medline CASGoogle Scholar
• 6 Bachmann BJ. Pedigrees of some mutant strains of Escherichia coli K-12. Bacteriol. Rev. 36(4), 525–557 (1972).
  Medline CASGoogle Scholar
• 7 Johnson JR, Moseley SL, Roberts PL, Stamm WE. Aerobactin and other virulence factor genes among strains of Escherichia coli causing urosepsis: association with patient characteristics. Infect. Immun. 56(2), 405–412 (1988).
  Medline CASGoogle Scholar
• 8 Johnson JR, Russo TA. Molecular epidemiology of extraintestinal pathogenic (uropathogenic) Escherichia coli. Int. J. Med. Microbiol. 295(6), 383–404 (2005).
  Medline CASGoogle Scholar
• 9 Parker KS, Wilson JD, Marschall J, Mucha PJ, Henderson JP. Network analysis reveals sex- and antibiotic resistance-associated antivirulence targets in clinical uropathogens. ACS Infect. Dis. 1(11), 523–532 (2015). • Uses contemporary network analyses to identify common virulence factor combinations in Escherichia coli from a large clinical cohort. Siderophore system combinations were representative of the resulting groups.
  Medline CASGoogle Scholar
• 10 Brumbaugh AR, Smith SN, Subashchandrabose S et al. Blocking yersiniabactin import attenuates extraintestinal pathogenic Escherichia coli in cystitis and pyelonephritis and represents a novel target to prevent urinary tract infection. Infect. Immun. 83(4), 1443–1450 (2015).
  Medline CASGoogle Scholar
• 11 Subashchandrabose S, Hazen TH, Brumbaugh AR et al. Host-specific induction of Escherichia coli fitness genes during human urinary tract infection. Proc. Natl Acad. Sci. USA 111(51), 18327–18332 (2014).
  Medline CASGoogle Scholar
• 12 Conover MS, Hadjifrangiskou M, Palermo JJ, Hibbing ME, Dodson KW, Hultgren SJ. Metabolic requirements of Escherichia coli in intracellular bacterial communities during urinary tract infection pathogenesis. mBio 7(2), e00104–e00116 (2016).
  Medline CASGoogle Scholar
• 13 Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM. Metal ions in biological catalysis: from enzyme databases to general principles. J. Biol. Inorg. Chem. 13(8), 1205–1218 (2008).
  Medline CASGoogle Scholar
• 14 Berg JM. Metal ions in proteins: structural and functional roles. Cold Spring Harb. Symp. Quant. Biol. 52, 579–585 (1987).
  Medline CASGoogle Scholar
• 15 Ballantine SP, Boxer DH. Nickel-containing hydrogenase isoenzymes from anaerobically grown Escherichia coli K-12. J. Bacteriol. 163(2), 454–459 (1985).
  Medline CASGoogle Scholar
• 16 Alteri CJ, Smith SN, Mobley HLT. Fitness of Escherichia coli during urinary tract infection requires gluconeogenesis and the TCA cycle. PLoS Pathog. 5(5), e1000448 (2009).
  MedlineGoogle Scholar
• 17 Winterbourn CC, Kettle AJ, Hampton MB. Reactive oxygen species and neutrophil function. Annu. Rev. Biochem. 85(1), 765–792 (2016).
  Medline CASGoogle Scholar
• 18 Imlay JA. Cellular defenses against superoxide and hydrogen peroxide. Annu. Rev. Biochem. 77(1), 755–776 (2008).
  Medline CASGoogle Scholar
• 19 Anjem A, Imlay JA. Mononuclear iron enzymes are primary targets of hydrogen peroxide stress. J. Biol. Chem. 287(19), 15544–15556 (2012).
  Medline CASGoogle Scholar
• 20 Anjem A, Varghese S, Imlay JA. Manganese import is a key element of the OxyR response to hydrogen peroxide in Escherichia coli. Mol. Microbiol. 72(4), 844–858 (2009).
  Medline CASGoogle Scholar
• 21 Rothen A. Ferritin and apoferritin in the ultracentrifuge: studies on the relationship of ferritin and apoferritin; precision measurements of the rates of sedimentation of apoferritin. J. Biol. Chem. 152(3), 679–693 (1944).
  CASGoogle Scholar
• 22 Shields-Cutler RR, Crowley JR, Hung CS et al. Human urinary composition controls antibacterial activity of siderocalin. J. Biol. Chem. 290(26), 15949–15960 (2015). •• Identifies a new mechanism of nutritional immunity in the presence of human urine that is counteracted by uropathogenic Escherichia coli (UPEC) siderophore expression.
  Medline CASGoogle Scholar
• 23 Hellman NE, Gitlin JD. Ceruloplasmin metabolism and function. Annu. Rev. Nutr. 22(1), 439–458 (2002).
  Medline CASGoogle Scholar
• 24 Puig S, Thiele DJ. Molecular mechanisms of copper uptake and distribution. Curr. Opin. Chem. Biol. 6(2), 171–180 (2002).
  Medline CASGoogle Scholar
• 25 Jeong J, Eide DJ. The SLC39 family of zinc transporters. Mol. Aspects Med. 34(2–3), 612–619 (2013).
  Medline CASGoogle Scholar
• 26 Palmiter RD, Huang L. Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers. Pflügers Arch. 447(5), 744–751 (2004).
  Medline CASGoogle Scholar
• 27 Wellenreuther G, Cianci M, Tucoulou R, Meyer-Klaucke W, Haase H. The ligand environment of zinc stored in vesicles. Biochem. Biophys. Res. Commun. 380(1), 198–203 (2009).
  Medline CASGoogle Scholar
• 28 Palmiter RD. The elusive function of metallothioneins. Proc. Natl Acad. Sci. USA 95(15), 8428–8430 (1998).
  Medline CASGoogle Scholar
• 29 Sieniawska CE, Jung LC, Olufadi R, Walker V. Twenty-four hour urinary trace element excretion: reference intervals and interpretive issues. Ann. Clin. Biochem. 49(4), 341–351 (2012).
  Medline CASGoogle Scholar
• 30 Hyre AN, Kavanagh K, Kock ND, Donati GL, Subashchandrabose S. Copper is a host effector mobilized to urine during urinary tract infection to impair bacterial colonization. Infect. Immun. 85(3), pii: e01041–16 (2017).
  MedlineGoogle Scholar
• 31 Meyer-Siegler KL, Iczkowski KA, Vera PL. Macrophage migration inhibitory factor is increased in the urine of patients with urinary tract infection: macrophage migration inhibitory factor–protein complexes in human urine. J. Urol. 175(4), 1523–1528 (2006).
  Medline CASGoogle Scholar
• 32 Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 102(3), 783–788 (2003).
  Medline CASGoogle Scholar
• 33 Arezes J, Jung G, Gabayan V et al. Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus. Cell Host Microbe 17(1), 47–57 (2015).
  Medline CASGoogle Scholar
• 34 Wessling-Resnick M. Nramp1 and other transporters involved in metal withholding during infection. J. Biol. Chem. 290(31), 18984–18990 (2015).
  Medline CASGoogle Scholar
• 35 Pan Y, Sonn GA, Sin MLY et al. Electrochemical immunosensor detection of urinary lactoferrin in clinical samples for urinary tract infection diagnosis. Biosens. Bioelectron. 26(2), 649–654 (2010).
  Medline CASGoogle Scholar
• 36 Wally J, Buchanan SK. A structural comparison of human serum transferrin and human lactoferrin. Biometals 20(3), 249 (2007).
  Medline CASGoogle Scholar
• 37 Reyes L, Alvarez S, Allam A, Reinhard M, Brown MB. Complicated urinary tract infection is associated with uroepithelial expression of proinflammatory protein S100A8. Infect. Immun. 77(10), 4265–4274 (2009).
  Medline CASGoogle Scholar
• 38 Corbin BD, Seeley EH, Raab A et al. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865), 962–965 (2008).
  Medline CASGoogle Scholar
• 39 Nakashige TG, Zhang B, Krebs C, Nolan EM. Human calprotectin is an iron-sequestering host-defense protein. Nat. Chem. Biol. 11(10), 765–771 (2015).
  Medline CASGoogle Scholar
• 40 Nakashige TG, Zygiel EM, Drennan CL, Nolan EM. Nickel sequestration by the host-defense protein human calprotectin. J. Am. Chem. Soc. 139(26), 8828–8836 (2017).
  Medline CASGoogle Scholar
• 41 Paragas N, Kulkarni R, Werth M et al. α-Intercalated cells defend the urinary system from bacterial infection. J. Clin. Invest. 124(7), 2963–2976 (2014).
  Medline CASGoogle Scholar
• 42 Correnti C, Strong RK. Mammalian siderophores, siderophore-binding lipocalins, and the labile iron pool. J. Biol. Chem. 287(17), 13524–13531 (2012).
  Medline CASGoogle Scholar
• 43 Reigstad CS, Hultgren SJ, Gordon JI. Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled. J. Biol. Chem. 282(29), 21259–21267 (2007).
  Medline CASGoogle Scholar
• 44 Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol. Cell. 10(5), 1033–1043 (2002).
  Medline CASGoogle Scholar
• 45 Flo TH, Smith KD, Sato S et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nat. Cell Biol. 432(7019), 917–921 (2004).
  CASGoogle Scholar
• 46 Shields-Cutler RR, Crowley JR, Miller CD, Stapleton AE, Cui W, Henderson JP. Human metabolome-derived cofactors are required for the antibacterial activity of siderocalin in urine. J. Biol. Chem. 291(50), 25901–25910 (2016). •• Demonstrates enterobactin production by UPEC in the presence of siderocalin during clinical urinary tract infection. Urinary metabolites are identified that are used by siderocalin to sequester ferric ions.
  Medline CASGoogle Scholar
• 47 Gilston BA, Wang S, Marcus MD et al. Structural and mechanistic basis of zinc regulation across the E. coli Zur regulon. PLoS Biol. 12(11), e1001987 (2014).
  MedlineGoogle Scholar
• 48 Chivers PT, Sauer RT. NikR repressor: high-affinity nickel binding to the C-terminal domain regulates binding to operator DNA. Chem. Biol. 9(10), 1141–1148 (2002).
  Medline CASGoogle Scholar
• 49 Waters LS, Sandoval M, Storz G. The Escherichia coli MntR miniregulon includes genes encoding a small protein and an efflux pump required for manganese homeostasis. J. Bacteriol. 193(21), 5887–5897 (2011).
  MedlineGoogle Scholar
• 50 Wurpel DJ, Moriel DG, Totsika M, Easton DM, Schembri MA. Comparative analysis of the uropathogenic Escherichia coli surface proteome by tandem mass-spectrometry of artificially induced outer membrane vesicles. J. Proteomics 115(C), 93–106 (2015).
  Google Scholar
• 51 Russo TA, Carlino UB, Johnson JR. Identification of a new iron-regulated virulence gene, ireA, in an extraintestinal pathogenic isolate of Escherichia coli. Infect. Immun. 69(10), 6209–6216 (2001).
  Medline CASGoogle Scholar
• 52 Ouyang Z, Isaacson R. Identification and characterization of a novel ABC iron transport system, Fit, in Escherichia coli. Infect. Immun. 74(12), 6949–6956 (2006).
  Medline CASGoogle Scholar
• 53 Snyder JA, Haugen BJ, Buckles EL et al. Transcriptome of uropathogenic Escherichia coli during urinary tract infection. Infect. Immun. 72(11), 6373–6381 (2004).
  Medline CASGoogle Scholar
• 54 Kammler M, Schön C, Hantke K. Characterization of the ferrous iron uptake system of Escherichia coli. J. Bacteriol. 175(19), 6212–6219 (1993).
  Medline CASGoogle Scholar
• 55 Hantke K. Is the bacterial ferrous iron transporter FeoB a living fossil? Trends Microbiol. 11(5), 192–195 (2003).
  Medline CASGoogle Scholar
• 56 Cao J, Woodhall MR, Alvarez J, Cartron ML, Andrews SC. EfeUOB (YcdNOB) is a tripartite, acid-induced and CpxAR-regulated, low-pH Fe²⁺ transporter that is cryptic in Escherichia coli K-12 but functional in E. coli O157:H7. Mol. Microbiol. 65(4), 857–875 (2007).
  Medline CASGoogle Scholar
• 57 Makui H, Roig E, Cole ST, Helmann JD, Gros P, Cellier MFM. Identification of the Escherichia coli K-12 Nramp orthologue (MntH) as a selective divalent metal ion transporter. Mol. Microbiol. 35(5), 1065–1078 (2000).
  Medline CASGoogle Scholar
• 58 Grass G, Franke S, Taudte N et al. The metal permease ZupT from Escherichia coli is a transporter with a broad substrate spectrum. J. Bacteriol. 187(5), 1604–1611 (2005).
  Medline CASGoogle Scholar
• 59 Sabri M, Léveillé S, Dozois CM. A SitABCD homologue from an avian pathogenic Escherichia coli strain mediates transport of iron and manganese and resistance to hydrogen peroxide. Microbiology 152(3), 745–758 (2006).
  Medline CASGoogle Scholar
• 60 Kehres DG, Janakiraman A, Slauch JM, Maguire ME. SitABCD is the alkaline Mn²⁺ transporter of Salmonella enterica serovar Typhimurium. J. Bacteriol. 184(12), 3159–3166 (2002).
  Medline CASGoogle Scholar
• 61 Gunasekera TS, Herre AH, Crowder MW. Absence of ZnuABC-mediated zinc uptake affects virulence-associated phenotypes of uropathogenic Escherichia coli CFT073 under Zn(II)-depleted conditions. FEMS Microbiol. Lett. 300(1), 36–41 (2009).
  Medline CASGoogle Scholar
• 62 Sabri M, Houle S, Dozois CM. Roles of the extraintestinal pathogenic Escherichia coli ZnuACB and ZupT zinc transporters during urinary tract infection. Infect. Immun. 77(3), 1155–1164 (2009).
  Medline CASGoogle Scholar
• 63 Wyckoff EE, Duncan D, Torres AG, Mills M, Maase K, Payne SM. Structure of the Shigella dysenteriae haem transport locus and its phylogenetic distribution in enteric bacteria. Mol. Microbiol. 28(6), 1139–1152 (1998).
  Medline CASGoogle Scholar
• 64 Nagy G, Dobrindt U, Kupfer M, Emody L, Karch H, Hacker J. Expression of hemin receptor molecule ChuA is influenced by RfaH in uropathogenic Escherichia coli strain 536. Infect. Immun. 69(3), 1924–1928 (2001).
  Medline CASGoogle Scholar
• 65 Hagan EC, Mobley HLT. Uropathogenic Escherichia coli outer membrane antigens expressed during urinary tract infection. Infect. Immun. 75(8), 3941–3949 (2007).
  Medline CASGoogle Scholar
• 66 Hagan EC, Mobley HLT. Haem acquisition is facilitated by a novel receptor Hma and required by uropathogenic Escherichia coli for kidney infection. Mol. Microbiol. 71(1), 79–91 (2009).
  Medline CASGoogle Scholar
• 67 Hagan EC, Lloyd AL, Rasko DA, Faerber GJ, Mobley HLT. Escherichia coli global gene expression in urine from women with urinary tract infection. PLoS Pathog. 6(11), e1001187 (2010). • Detects transcriptional activation of siderophore systems in E. coli directly recovered from UTI patients.
  MedlineGoogle Scholar
• 68 Wagegg W, Braun V. Ferric citrate transport in Escherichia coli requires outer membrane receptor protein fecA. J. Bacteriol. 145(1), 156–163 (1981).
  Medline CASGoogle Scholar
• 69 Pressler U, Staudenmaier H, Zimmermann L, Braun V. Genetics of the iron dicitrate transport system of Escherichia coli. J. Bacteriol. 170(6), 2716–2724 (1988).
  Medline CASGoogle Scholar
• 70 Staudenmaier H, Van Hove B, Yaraghi Z, Braun V. Nucleotide sequences of the fecBCDE genes and locations of the proteins suggest a periplasmic-binding-protein-dependent transport mechanism for iron(III) dicitrate in Escherichia coli. J. Bacteriol. 171(5), 2626–2633 (1989).
  Medline CASGoogle Scholar
• 71 Kadner RJ, Heller K, Coulton JW, Braun V. Genetic control of hydroxamate-mediated iron uptake in Escherichia coli. J. Bacteriol. 143(1), 256–264 (1980).
  Medline CASGoogle Scholar
• 72 Hantke K. Identification of an iron uptake system specific for coprogen and rhodotorulic acid in Escherichia coli K12. Mol. Gen. Genet. 191(2), 301–306 (1983).
  Medline CASGoogle Scholar
• 73 Braun V, Brazel-Faisst C, Schneider R. Growth stimulation of Escherichia coli in serum by iron(III) aerobactin. Recycling of aerobactin. FEMS Microbiol. Lett. 21(1), 99–103 (1984).
  CASGoogle Scholar
• 74 Chen SL, Hung C-S, Xu J et al. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. Proc. Natl Acad. Sci. USA 103(15), 5977–5982 (2006).
  Medline CASGoogle Scholar
• 75 Neilands JB. Siderophores: structure and function of microbial iron transport compounds. J. Biol. Chem. 270(45), 26723–26726 (1995).
  Medline CASGoogle Scholar
• 76 Henderson JP, Crowley JR, Pinkner JS et al. Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli. PLoS Pathog. 5(2), e1000305 (2009).
  MedlineGoogle Scholar
• 77 Podschun R, Sievers D, Fischer A, Ullmann U. Serotypes, hemagglutinins, siderophore synthesis, and serum resistance of Klebsiella isolates causing human urinary tract infections. J. Infect. Dis. 168(6), 1415–1421 (1993).
  Medline CASGoogle Scholar
• 78 Mokracka J, Koczura R, Kaznowski A. Yersiniabactin and other siderophores produced by clinical isolates of Enterobacter spp. and Citrobacter spp. FEMS Immunol. Med. Microbiol. 40(1), 51–55 (2004).
  Medline CASGoogle Scholar
• 79 Rutz JM, Abdullah T, Singh SP, Kalve VI, Klebba PE. Evolution of the ferric enterobactin receptor in Gram-negative bacteria. J. Bacteriol. 173(19), 5964–5974 (1991).
  Medline CASGoogle Scholar
• 80 Cooper SR, McArdle JV, Raymond KN. Siderophore electrochemistry: relation to intracellular iron release mechanism. Proc. Natl Acad. Sci. USA 75(8), 3551–3554 (1978).
  Medline CASGoogle Scholar
• 81 Hantke K. Dihydroxybenzolyserine – a siderophore for E. coli. FEMS Microbiol. Lett. 67(1), 5–8 (1990).
  CASGoogle Scholar
• 82 Hantke K, Nicholson G, Rabsch W, Winkelmann G. Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN. Proc. Natl Acad. Sci. USA 100(7), 3677–3682 (2003).
  Medline CASGoogle Scholar
• 83 Bister B, Bischoff D, Nicholson GJ et al. The structure of salmochelins: C-glucosylated enterobactins of Salmonella enterica. Biometals. 17(4), 471–481 (2004).
  Medline CASGoogle Scholar
• 84 Johnson JR, Russo TA, Tarr PI et al. Molecular epidemiological and phylogenetic associations of two novel putative virulence genes, iha and iroN(E. coli), among Escherichia coli isolates from patients with urosepsis. Infect. Immun. 68(5), 3040–3047 (2000).
  Medline CASGoogle Scholar
• 85 Lin H, Fischbach MA, Liu DR, Walsh CT. In vitro characterization of salmochelin and enterobactin trilactone hydrolases IroD, IroE, and Fes. J. Am. Chem. Soc. 127(31), 11075–11084 (2005).
  Medline CASGoogle Scholar
• 86 Zhu M, Valdebenito M, Winkelmann G, Hantke K. Functions of the siderophore esterases IroD and IroE in iron-salmochelin utilization. Microbiology 151(7), 2363–2372 (2005).
  Medline CASGoogle Scholar
• 87 Crouch M-LV, Castor M, Karlinsey JE, Kalhorn T, Fang FC. Biosynthesis and IroC-dependent export of the siderophore salmochelin are essential for virulence of Salmonella enterica serovar Typhimurium. Mol. Microbiol. 67(5), 971–983 (2008).
  Medline CASGoogle Scholar
• 88 Johnson JR, Scheutz F, Ulleryd P, Kuskowski MA, O'Bryan TT, Sandberg T. Phylogenetic and pathotypic comparison of concurrent urine and rectal Escherichia coli isolates from men with febrile urinary tract infection. J. Clin. Microbiol. 43(8), 3895–3900 (2005).
  Medline CASGoogle Scholar
• 89 Lv H, Hung CS, Henderson JP. Metabolomic analysis of siderophore cheater mutants reveals metabolic costs of expression in uropathogenic Escherichia coli. J. Proteome Res. 13(3), 1397–1404 (2014).
  Medline CASGoogle Scholar
• 90 Konopka K, Neilands JB. Effect of serum albumin on siderophore-mediated utilization of transferrin iron. Biochemistry 23(10), 2122–2127 (1984).
  Medline CASGoogle Scholar
• 91 Luo M, Lin H, Fischbach MA, Liu DR, Walsh CT, Groves JT. Enzymatic tailoring of enterobactin alters membrane partitioning and iron acquisition. ACS Chem. Biol. 1(1), 29–32 (2006).
  Medline CASGoogle Scholar
• 92 Fischbach MA, Lin H, Zhou L et al. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc. Natl Acad. Sci. USA 103(44), 16502–16507 (2006).
  Medline CASGoogle Scholar
• 93 Magistro G, Hoffmann C, Schubert S. The salmochelin receptor IroN itself, but not salmochelin-mediated iron uptake promotes biofilm formation in extraintestinal pathogenic Escherichia coli (ExPEC). Int. J. Med. Microbiol. 305(4–5), 435–445 (2015).
  Medline CASGoogle Scholar
• 94 Feldmann F, Sorsa LJ, Hildinger K, Schubert S. The salmochelin siderophore receptor IroN contributes to invasion of urothelial cells by extraintestinal pathogenic Escherichia coli in vitro. Infect. Immun. 75(6), 3183–3187 (2007).
  Medline CASGoogle Scholar
• 95 Russo TA, McFadden CD, Carlino-MacDonald UB, Beanan JM, Barnard TJ, Johnson JR. IroN functions as a siderophore receptor and is a urovirulence factor in an extraintestinal pathogenic isolate of Escherichia coli. Infect. Immun. 70(12), 7156–7160 (2002).
  Medline CASGoogle Scholar
• 96 Steigedal M, Marstad A, Haug M et al. Lipocalin 2 imparts selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infection. J. Immunol. 193(12), 6081–6089 (2014).
  Medline CASGoogle Scholar
• 97 Gibson F, Magrath DI. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62–1. Biochim. Biophys. Acta 192(2), 175–184 (1969).
  Medline CASGoogle Scholar
• 98 Schmidt H, Hensel M. Pathogenicity islands in bacterial pathogenesis. Clin. Microbiol. Rev. 17(1), 14–56 (2004).
  Medline CASGoogle Scholar
• 99 Harris WR, Carrano CJ, Raymond KN. Coordination chemistry of microbial iron transport compounds. 16. Isolation, characterization, and formation constants of ferric aerobactin. J. Am. Chem. Soc. 101(10), 2722–2727 (1979).
  CASGoogle Scholar
• 100 de Lorenzo V, Martinez JL. Aerobactin production as a virulence factor: a reevaluation. Eur. J. Clin. Microbiol. Infect. Dis. 7(5), 621–629 (1988).
  Medline CASGoogle Scholar
• 101 Soto SM, Smithson A, Horcajada JP, Martinez JA, Mensa JP, Vila J. Implication of biofilm formation in the persistence of urinary tract infection caused by uropathogenic Escherichia coli. Clin. Microbiol. Infect. 12(10), 1034–1036 (2006).
  Medline CASGoogle Scholar
• 102 Johnson JR, O'Bryan TT, Delavari P et al. Clonal relationships and extended virulence genotypes among Escherichia coli isolates from women with a first or recurrent episode of cystitis. J. Infect. Dis. 183(10), 1508–1517 (2001).
  Medline CASGoogle Scholar
• 103 Johnson JR, Porter S, Thuras P, Castanheira M. The pandemic H30 subclone of sequence type 131 (ST131) as the leading cause of multidrug-resistant Escherichia coli infections in the United States (2011–2012). Open Forum Infect. Dis. 4(2), ofx089 (2017).
  MedlineGoogle Scholar
• 104 Torres AG, Redford P, Welch RA, Payne SM. TonB-dependent systems of uropathogenic Escherichia coli: aerobactin and heme transport and TonB are required for virulence in the mouse. Infect. Immun. 69(10), 6179–6185 (2001).
  Medline CASGoogle Scholar
• 105 Garcia EC, Brumbaugh AR, Mobley HLT. Redundancy and specificity of Escherichia coli iron acquisition systems during urinary tract infection. Infect. Immun. 79(3), 1225–1235 (2011).
  Medline CASGoogle Scholar
• 106 Konopka K, Bindereif A, Neilands JB. Aerobactin-mediated utilization of transferrin iron. Biochemistry 21(25), 6503–6508 (1982).
  Medline CASGoogle Scholar
• 107 Valdebenito M, Crumbliss AL, Winkelmann G, Hantke K. Environmental factors influence the production of enterobactin, salmochelin, aerobactin, and yersiniabactin in Escherichia coli strain Nissle 1917. Int. J. Med. Microbiol. 296(8), 513–520 (2006).
  Medline CASGoogle Scholar
• 108 Perry RD, Fetherston JD. Yersiniabactin iron uptake: mechanisms and role in Yersinia pestis pathogenesis. Microbes Infect. 13(10), 808–817 (2011).
  Medline CASGoogle Scholar
• 109 Fetherston JD, Bearden SW, Perry RD. YbtA, an AraC-type regulator of the Yersinia pestis pesticin/yersiniabactin receptor. Mol. Microbiol. 22(2), 315–325 (1996).
  Medline CASGoogle Scholar
• 110 Miller MC, Parkin S, Fetherston JD, Perry RD, DeMoll E. Crystal structure of ferric-yersiniabactin, a virulence factor of Yersinia pestis. J. Inorg. Biochem. 100(9), 1495–1500 (2006).
  Medline CASGoogle Scholar
• 111 Ohlemacher SI, Giblin DE, d'Avignon DA, Stapleton AE, Trautner BW, Henderson JP. Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J. Clin. Invest. 127(11), 4018–4030 (2017). •• Identifies escherichelin as an additional siderophore-like cellular product of Yersinia high pathogenicity island that acts as an inhibitor of the virulence-associated pyochelin siderophore system in Pseudomonas.
  MedlineGoogle Scholar
• 112 Koh E-I, Robinson AE, Bandara N, Rogers BE, Henderson JP. Copper import in Escherichia coli by the yersiniabactin metallophore system. Nat. Chem. Biol. 13, 1016–1021 (2017). •• Establishes yersiniabactin as a metallophore capable of importing both iron and copper ions for nutritional use.
  Medline CASGoogle Scholar
• 113 Chaturvedi KS, Hung CS, Crowley JR, Stapleton AE, Henderson JP. The siderophore yersiniabactin binds copper to protect pathogens during infection. Nat. Chem. Biol. 8(8), 731–736 (2012). •• Identifies a noncanonical role for yersiniabactin as a copper ligand during clinical UTI. Supports UPEC copper sequestration to resist copper toxicity as a virulence strategy.
  Medline CASGoogle Scholar
• 114 Koh E-I, Hung CS, Henderson JP. The yersiniabactin-associated ATP binding cassette proteins YbtP and YbtQ enhance Escherichia coli fitness during high-titer cystitis. Infect. Immun. 84(5), 1312–1319 (2016).
  Medline CASGoogle Scholar
• 115 Bachman MA, Oyler JE, Burns SH et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect. Immun. 79(8), 3309–3316 (2011).
  Medline CASGoogle Scholar
• 116 Koh E-I, Hung CS, Parker KS, Crowley JR, Giblin DE, Henderson JP. Metal selectivity by the virulence-associated yersiniabactin metallophore system. Metallomics 7, 1011–1022 (2015).
  Medline CASGoogle Scholar
• 117 Bobrov AG, Kirillina O, Fetherston JD, Miller MC, Burlison JA, Perry RD. The Yersinia pestis siderophore, yersiniabactin, and the ZnuABC system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice. Mol. Microbiol. 93(4), 759–775 (2014).
  Medline CASGoogle Scholar
• 118 Bobrov AG, Kirillina O, Fosso MY et al. Zinc transporters YbtX and ZnuABC are required for the virulence of Yersinia pestis in bubonic and pneumonic plague in mice. Metallomics 9(6), 757–772 (2017).
  Medline CASGoogle Scholar
• 119 Macomber L, Imlay JA. The iron–sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. Proc. Natl Acad. Sci. USA 106(20), 8344–8349 (2009).
  Medline CASGoogle Scholar
• 120 Koh E-I, Henderson JP. Microbial copper-binding siderophores at the host–pathogen interface. J. Biol. Chemis. 290(31), 18967–18974 (2015).
  Medline CASGoogle Scholar
• 121 Chaturvedi KS, Henderson JP. Pathogenic adaptations to host-derived antibacterial copper. Front. Cell. Infect. Microbiol. 4, 3 (2014).
  MedlineGoogle Scholar
• 122 White C, Lee J, Kambe T, Fritsche K, Petris MJ. A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J. Biol. Chem. 284(49), 33949–33956 (2009).
  Medline CASGoogle Scholar
• 123 Chaturvedi KS, Hung CS, Giblin DE et al. Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic. ACS Chem. Biol. 9(2), 551–561 (2013). •• Observes yersiniabactin-mediated protection of UPEC during phagocytosis in the presence of copper ions, supporting a noncanonical cytoprotective role for this metallophore.
  MedlineGoogle Scholar
• 124 Mislin GL, Burger A, Abdallah MA. Synthesis of new thiazole analogues of pyochelin, a siderophore of Pseudomonas aeruginosa and Burkholderia cepacia. A new conversion of thiazolines into thiazoles. Tetrahedron 60(52), 12139–12145 (2004).
  CASGoogle Scholar
• 125 Mislin GLA, Hoegy F, Cobessi D, Poole K, Rognan D, Schalk IJ. Binding properties of pyochelin and structurally related molecules to FptA of Pseudomonas aeruginosa. J. Mol. Biol. 357(5), 1437–1448 (2006).
  Medline CASGoogle Scholar
• 126 Bitsori M, Maraki S, Koukouraki S, Galanakis E. Pseudomonas Aeruginosa urinary tract infection in children: risk factors and outcomes. J. Urol. 187(1), 260–264 (2012).
  Medline CASGoogle Scholar
• 127 Horwitz D, McCue T, Mapes AC et al. Decreased microbiota diversity associated with urinary tract infection in a trial of bacterial interference. J. Infect. 71(3), 358–367 (2015).
  MedlineGoogle Scholar
• 128 Bohac TJ, Shapiro JA, Wencewicz TA. Rigid oxazole acinetobactin analog blocks siderophore cycling in Acinetobacter baumannii. ACS Infect. Dis. 3(11), 802–806 (2017).
  Medline CASGoogle Scholar