Advertisement

Antibacterials pp 151-183 | Cite as

Sideromycins as Pathogen-Targeted Antibiotics

Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 26)

Abstract

The overuse of broad-spectrum antibiotics rapidly selects for dangerous multi-drug resistant bacterial pathogens. The landscape of antibiotic drug discovery is adapting to this wave of resistance with a movement towards narrow-spectrum, pathogen-targeted antibiotics that limit the emergence of new resistance. Sideromycins (siderophore-antibiotic conjugates) exploit essential iron acquisition pathways to achieve receptor-mediated cell entry where the spectrum of antibiotic activity is determined by highly selective cell surface siderophore receptors rather than the widely distributed and highly conserved antibacterial target. Sideromycins overwhelm traditional resistance mechanisms through high intracellular antibiotic concentrations and resistance adaptation renders pathogens avirulent. The timing is optimal to pursue sideromycins as pathogen-targeted antibiotics and chemical probes for rapid pathogen diagnostics.

Keywords

Albomycin Antibiotic-delivery systems Baulamycin Enterobactin Grisein Microcin Mycobactin Pyoverdine Salmycin Sideromycin Staphyloferrin Tetroazolemycin Trojan horse Xenosiderophore 

Notes

Acknowledgments

MJM thanks all group members and collaborators who worked on the synthesis and study of siderophores and sideromycins in his research laboratory at the University of Notre Dame over the past 40 years (1977–2017) with near continuous support from the NIH. MJM and TAW sincerely thank Dr. Ute Möllmann (Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute) for years of friendship and collaboration on siderophore microbiology. TAW acknowledges the NSF for a CAREER Award (1654611) that supports siderophore research in his laboratory.

References

  1. 1.
    Walsh C, Wencewicz T (2016) Antibiotics: challenges, mechanisms, opportunities. ASM Press, Washington, DCGoogle Scholar
  2. 2.
    Brown ED, Wright GD (2016) Antibacterial drug discovery in the resistance era. Nature 529:336–343. doi: 10.1038/nature17042CrossRefPubMedGoogle Scholar
  3. 3.
    Wencewicz TA (2016) New antibiotics from nature’s chemical inventory. Bioorg Med Chem 24:6227–6252. doi: 10.1016/j.bmc.2016.09.014CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Maxson T, Mitchell DA (2016) Targeted treatment for bacterial infections: prospects for pathogen-specific antibiotics coupled with rapid diagnostics. Tetrahedron 72:3609–3624. doi: 10.1016/j.tet.2015.09.069CrossRefPubMedGoogle Scholar
  5. 5.
    Delcour AH (2009) Outer membrane permeability and antibiotic resistance. Biochim Biophys Acta 1794:808–816. doi: 10.1016/j.bbapap.2008.11.005CrossRefPubMedGoogle Scholar
  6. 6.
    Zgurskaya HI, Lopez CA, Gnanakaran S (2015) Permeability barrier of Gram-negative cell envelopes and approaches to bypass it. ACS Infect Dis 1:512–522. doi: 10.1021/acsinfecdis.5b00097CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Skwarecki AS, Milewski S, Schielmann M, Milewska MJ (2016) Antimicrobial molecular nanocarrier–drug conjugates. Nanomed Nanotech Biol Med 12:2215–2240. doi: 10.1016/j.nano.2016.06.002CrossRefGoogle Scholar
  8. 8.
    Hart KM, Reck M, Bowman GR, Wencewicz TA (2016) Tabtoxinine-β-lactam is a “stealth” β-lactam antibiotic that evades β-lactamase-mediated antibiotic resistance. Med Chem Commun 7:118–127. doi: 10.1039/C5MD00325CCrossRefGoogle Scholar
  9. 9.
    Pereira MP, Kelley SO (2011) Maximizing the therapeutic window of an antimicrobial drug by imparting mitochondrial sequestration in human cells. J Am Chem Soc 133:3260–3263. doi: 10.1021/ja110246uCrossRefPubMedGoogle Scholar
  10. 10.
    Jung ME, Yang EC, Vu BT, Kiankarimi M, Spyrou E, Kaunitz J (1999) Glycosylation of fluoroquinolones through direct and oxygenated polymethylene linkages as a sugar-mediated active transport system for antimicrobials. J Med Chem 42:3899–3909. doi: 10.1021/jm990015bCrossRefPubMedGoogle Scholar
  11. 11.
    Abed N, Said-Hassane F, Zouhiri F, Mougin J, Nicolas V, Desmaele D, Gref R, Couvreur P (2015) An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance. Sci Rep 5:13500. doi: 10.1038/srep13500CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Stebbins ND, Ouimet MA, Uhrich KE (2014) Antibiotic-containing polymers for localized, sustained drug delivery. Adv Drug Deliv Rev 78:77–87. doi: 10.1016/j.addr.2014.04.006CrossRefPubMedGoogle Scholar
  13. 13.
    Xiong M-H, Bao Y, Yang X-Z, Zhu Y-H, Wang J (2014) Delivery of antibiotics with polymeric particles. Adv Drug Deliv Rev 78:63–76. doi: 10.1016/j.addr.2014.02.002CrossRefPubMedGoogle Scholar
  14. 14.
    Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, DePalatis L, Raab H, Hazenbos WL, Hiroshi Morisaki J, Kim J, Park S, Darwish M, Lee B-C, Hernandez H, Loyet KM, Lupardus P, Fong R, Yan D, Chalouni C, Luis E, Khalfin Y, Plise E, Cheong J, Lyssikatos JP, Strandh M, Koefoed K, Andersen PS, Flygare JA, Wah Tan M, Brown EJ, Mariathasan S (2015) Novel antibody–antibiotic conjugate eliminates intracellular S. aureus. Nature 527:323–328. doi: 10.1038/nature16057CrossRefPubMedGoogle Scholar
  15. 15.
    Roosenberg II JM, Lin YM, Lu Y, Miller MJ (2000) Studies and syntheses of siderophores, microbial iron chelators, and analogs as potential drug delivery agents. Curr Med Chem 7:159–197. doi: 10.2174/0929867003375353CrossRefPubMedGoogle Scholar
  16. 16.
    Wanner S, Schade J, Keinhörster D, Weller N, George SE, Kull L, Bauer J, Grau T, Winstel V, Stoy H, Kretschmer D, Kolata J, Wolz C, Bröker BM, Weidenmaier C (2017) Wall teichoic acids mediate increased virulence in Staphylococcus aureus. Nat Microbiol 2:16257. doi: 10.1038/nmicrobiol.2016.257CrossRefPubMedGoogle Scholar
  17. 17.
    Rasko DA, Sperandio V (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat Rev Drug Discov 9:117–128. doi: 10.1038/nrd3013CrossRefPubMedGoogle Scholar
  18. 18.
    Braun V, Pramanik A, Gwinner T, Koberle M, Bohn E (2009) Sideromycins: tools and antibiotics. Biometals 22:3–13. doi: 10.1007/s10534-008-9199-7CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Palmer LD, Skaar EP (2016) Transition metals and virulence in bacteria. Annu Rev Genet 50:67–91. doi: 10.1146/annurev-genet-120215-035146CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Skaar EP (2010) The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog 6:e1000949. doi: 10.1371/journal.ppat.1000949CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lau CK, Krewulak KD, Vogel HJ (2016) Bacterial ferrous iron transport: the Feo system. FEMS Microbiol Rev 40:273–298. doi: 10.1093/femsre/fuv049CrossRefPubMedGoogle Scholar
  22. 22.
    Morgenthau A, Pogoutse A, Adamiak P, Moraes TF, Schryvers AB (2013) Bacterial receptors for host transferrin and lactoferrin: molecular mechanisms and role in host-microbe interactions. Future Microbiol 8:1575–1585. doi: 10.2217/fmb.13.125CrossRefPubMedGoogle Scholar
  23. 23.
    Contreras H, Chim N, Credali A, Goulding CW (2014) Heme uptake in bacterial pathogens. Curr Opin Chem Biol 19:34–41. doi: 10.1016/j.cbpa.2013.12.014CrossRefPubMedGoogle Scholar
  24. 24.
    Hider RC, Kong X (2010) Chemistry and biology of siderophores. Nat Prod Rep 27:637–657. doi: 10.1039/b906679aCrossRefPubMedGoogle Scholar
  25. 25.
    Holden VI, Bachman MA (2015) Diverging roles of bacterial siderophores during infection. Metallomics 7:986–995. doi: 10.1039/c4mt00333kCrossRefPubMedGoogle Scholar
  26. 26.
    Clifton MC, Corrent C, Strong RK (2009) Siderocalins: siderophore-binding proteins of the innate immune system. Biometals 22:557–564. doi: 10.1007/s10534-009-9207-6CrossRefPubMedGoogle Scholar
  27. 27.
    Shields-Cutler RR, Crowley JR, Hung CS, Stapleton AE, Aldrich CC, Marschall J, Henderson JP (2015) Human urinary composition controls siderocalin’s antibacterial activity. J Biol Chem 290:15949–15960. doi: 10.1074/jbc.M115.645812CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Shields-Cutler RR, Crowley JR, Miller CD, Stapleton AE, Cui W, Henderson JP (2016) Human metabolome-derived cofactors are required for the antibacterial activity of siderocalin in urine. J Biol Chem 291:25901–25910. doi: 10.1074/jbc.M116.759183CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Abergel RJ, Wilson MK, Arceneaux JE, Hoette TM, Strong RK, Byers BR, Raymond KN (2006) Anthrax pathogen evades the mammalian immune system through stealth siderophore production. Proc Natl Acad Sci U S A 103:18499–18503. doi: 10.1073/pnas.0607055103CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Abergel RJ, Moore EG, Strong RK, Raymond KN (2006) Microbial evasion of the immune system: structural modifications of enterobactin impair siderocalin recognition. J Am Chem Soc 128:10998–10999. doi: 10.1021/ja062476+CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Fischbach MA, Lin H, Liu DR, Walsh CT (2006) How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat Chem Biol 2:132–138. doi: 10.1038/nchembio771CrossRefPubMedGoogle Scholar
  32. 32.
    King AM, Reid-Yu SA, Wang W, King DT, De Pascale G, Strynadka NC, Walsh TR, Coombes BK, Wright GD (2014) Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance. Nature 510:503–506. doi: 10.1038/nature13445CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chan AN, Shiver AL, Wever WJ, Razvi SZA, Traxler MF, Li B (2017) Role for dithiolopyrrolones in disrupting bacterial metal homeostasis. Proc Natl Acad Sci U S A 114:2717–2722. doi: 10.1073/pnas.1612810114CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Lamb AL (2015) Breaking a pathogen’s iron will: inhibiting siderophore production as an antimicrobial strategy. Biochim Biophys Acta 1854:1054–1070. doi: 10.1016/j.bbapap.2015.05.001CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Neres J, Engelhart CA, Drake EJ, Wilson DJ, Fu P, Boshoff HI, Barry 3rd CE, Gulick AM, Aldrich CC (2013) Non-nucleoside inhibitors of BasE, an adenylating enzyme in the siderophore biosynthetic pathway of the opportunistic pathogen Acinetobacter baumannii. J Med Chem 56:2385–2405. doi: 10.1021/jm301709sCrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Wurst JM, Drake EJ, Theriault JR, Jewett IT, VerPlank L, Perez JR, Dandapani S, Palmer M, Moskowitz SM, Schreiber SL, Munoz B, Gulick AM (2014) Identification of inhibitors of PvdQ, an enzyme involved in the synthesis of the siderophore pyoverdine. ACS Chem Biol 9:1536–1544. doi: 10.1021/cb5001586CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Martín del Campo JS, Vogelaar N, Tolani K, Kizjakina K, Harich K, Sobrado P (2016) Inhibition of the flavin-dependent monooxygenase siderophore A (SidA) blocks siderophore biosynthesis and aspergillus fumigatus growth. ACS Chem Biol 11:3035–3042. doi: 10.1021/acschembio.6b00666CrossRefPubMedGoogle Scholar
  38. 38.
    Manos-Turvey A, Bulloch EM, Rutledge PJ, Baker EN, Lott JS, Payne RJ (2010) Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI). ChemMedChem 5:1067–1079. doi: 10.1002/cmdc.201000137CrossRefPubMedGoogle Scholar
  39. 39.
    Strauss E, Begley TP (2002) The antibiotic activity of N-pentylpantothenamide results from its conversion to ethyldethia-coenzyme A, a coenzyme A antimetabolite. J Biol Chem 277:48205–48209. doi: 10.1074/jbc.M204560200CrossRefPubMedGoogle Scholar
  40. 40.
    Virga KG, Zhang Y-M, Leonardi R, Ivey RA, Hevener K, Park H-W, Jackowski S, Rock CO, Lee RE (2006) Structure–activity relationships and enzyme inhibition of pantothenamide-type pantothenate kinase inhibitors. Bioorg Med Chem 14:1007–1020. doi: 10.1016/j.bmc.2005.09.021CrossRefPubMedGoogle Scholar
  41. 41.
    van der Westhuyzen R, Hammons Justin C, Meier Jordan L, Dahesh S, Moolman Wessel JA, Pelly Stephen C, Nizet V, Burkart Michael D, Strauss E (2012) The antibiotic CJ-15,801 is an antimetabolite that hijacks and then inhibits CoA biosynthesis. Chem Biol 19:559–571. doi: 10.1016/j.chembiol.2012.03.013CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Dale SE, Doherty-Kirby A, Lajoie G, Heinrichs DE (2004) Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Infect Immun 72:29–37. doi: 10.1128/IAI.72.1.29-37.2004CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Tripathi A, Schofield MM, Chlipala GE, Schultz PJ, Yim I, Newmister SA, Nusca TD, Scaglione JB, Hanna PC, Tamayo-Castillo G, Sherman DH (2014) Baulamycins A and B, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in Staphylococcus aureus and Bacillus anthracis. J Am Chem Soc 136:1579–1586. doi: 10.1021/ja4115924CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Ankenbauer RG, Staley AL, Rinehart KL, Cox CD (1991) Mutasynthesis of siderophore analogues by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 88:1878–1882CrossRefGoogle Scholar
  45. 45.
    Brown KA, Ratledge C (1975) The effect of p-aminosalicyclic acid on iron transport and assimilation in mycobacteria. Biochim Biophys Acta 385:207–220CrossRefGoogle Scholar
  46. 46.
    Challis GL, Hopwood DA (2003) Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc Natl Acad Sci U S A 100:14555–14561. doi: 10.1073/pnas.1934677100CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Xu Y, Miller MJ (1998) Total syntheses of mycobactin analogues as potent antimycobacterial agents using a minimal protecting group strategy. J Org Chem 63:4314–4322. doi: 10.1021/jo980063oCrossRefGoogle Scholar
  48. 48.
    Juarez-Hernandez RE, Franzblau SG, Miller MJ (2012) Syntheses of mycobactin analogs as potent and selective inhibitors of Mycobacterium tuberculosis. Org Biomol Chem 10:7584–7593. doi: 10.1039/c2ob26077hCrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Jones CM, Wells RM, Madduri AV, Renfrow MB, Ratledge C, Moody DB, Niederweis M (2014) Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling. Proc Natl Acad Sci U S A 111:1945–1950. doi: 10.1073/pnas.1311402111CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Yep A, McQuade T, Kirchhoff P, Larsen M, Mobley HLT (2014) Inhibitors of TonB function identified by a high-throughput screen for inhibitors of iron acquisition in uropathogenic Escherichia coli CFT073. MBio 5:e01089–e01013. doi: 10.1128/mBio.01089-13CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Hanson M, Jordan LD, Shipelskiy Y, Newton SM, Klebba PE (2016) High-throughput screening assay for inhibitors of TonB-dependent iron transport. J Biomol Screen 21:316–322. doi: 10.1177/1087057115613788CrossRefPubMedGoogle Scholar
  52. 52.
    Banin E, Lozinski A, Brady KM, Berenshtein E, Butterfield PW, Moshe M, Chevion M, Greenberg EP, Banin E (2008) The potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent. Proc Natl Acad Sci U S A 105:16761–16766. doi: 10.1073/pnas.0808608105CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Minandri F, Bonchi C, Frangipani E, Imperi F, Visca P (2014) Promises and failures of gallium as an antibacterial agent. Future Microbiol 9:379–397. doi: 10.2217/fmb.14.3CrossRefPubMedGoogle Scholar
  54. 54.
    Furci LM, Lopes P, Eakanunkul S, Zhong S, MacKerell AD, Wilks A (2007) Inhibition of the bacterial heme oxygenases from Pseudomonas aeruginosa and Neisseria meningitidis: novel antimicrobial targets. J Med Chem 50:3804–3813. doi: 10.1021/jm0700969CrossRefPubMedGoogle Scholar
  55. 55.
    Shirataki C, Shoji O, Terada M, Ozaki S, Sugimoto H, Shiro Y, Watanabe Y (2014) Inhibition of heme uptake in Pseudomonas aeruginosa by its hemophore (HasAp) bound to synthetic metal complexes. Angew Chem Int Ed 53:2862–2866. doi: 10.1002/anie.201307889CrossRefGoogle Scholar
  56. 56.
    Bergeron RJ, Bharti N, Singh S, McManis JS, Wiegand J, Green LG (2009) Vibriobactin antibodies: a vaccine strategy. J Med Chem 52:3801–3813. doi: 10.1021/jm900119qCrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Mike LA, Smith SN, Sumner CA, Eaton KA, Mobley HL (2016) Siderophore vaccine conjugates protect against uropathogenic Escherichia coli urinary tract infection. Proc Natl Acad Sci U S A 113:13468–13473. doi: 10.1073/pnas.1606324113CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Sassone-Corsi M, Chairatana P, Zheng T, Perez-Lopez A, Edwards RA, George MD, Nolan EM, Raffatellu M (2016) Siderophore-based immunization strategy to inhibit growth of enteric pathogens. Proc Natl Acad Sci U S A 113:13462–13467. doi: 10.1073/pnas.1606290113CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Bolin CA, Jensen AE (1987) Passive immunization with antibodies against iron-regulated outer membrane proteins protects turkeys from Escherichia coli septicemia. Infect Immun 55:1239–1242PubMedPubMedCentralGoogle Scholar
  60. 60.
    Clifton-Hadley FA, Breslin M, Venables LM, Sprigings KA, Cooles SW, Houghton S, Woodward MJ (2002) A laboratory study of an inactivated bivalent iron restricted Salmonella enterica serovars Enteritidis and Typhimurium dual vaccine against Typhimurium challenge in chickens. Vet Microbiol 89:167–179. doi: 10.1016/S0378-1135(02)00169-4CrossRefPubMedGoogle Scholar
  61. 61.
    Brumbaugh AR, Smith SN, Mobley HL (2013) Immunization with the yersiniabactin receptor, FyuA, protects against pyelonephritis in a murine model of urinary tract infection. Infect Immun 81:3309–3316. doi: 10.1128/iai.00470-13CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Mariotti P, Malito E, Biancucci M, Lo Surdo P, Mishra RP, Nardi-Dei V, Savino S, Nissum M, Spraggon G, Grandi G, Bagnoli F, Bottomley MJ (2013) Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2. Biochem J 449:683–693. doi: 10.1042/bj20121426CrossRefPubMedGoogle Scholar
  63. 63.
    Boiteau RM, Mende DR, Hawco NJ, McIlvin MR, Fitzsimmons JN, Saito MA, Sedwick PN, DeLong EF, Repeta DJ (2016) Siderophore-based microbial adaptations to iron scarcity across the eastern Pacific Ocean. Proc Natl Acad Sci U S A 113:14237–14242. doi: 10.1073/pnas.1608594113CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Crosa JH, Walsh CT (2002) Genetics and assembly line enzymology of siderophore biosynthesis in bacteria. Microbiol Mol Biol Rev 66:223–249. doi: 10.1128/MMBR.66.2.223-249.2002CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Abergel RJ, Raymond KN (2008) Terephthalamide-containing ligands: fast removal of iron from transferrin. J Biol Inorg Chem 13:229–240. doi: 10.1007/s00775-007-0314-yCrossRefPubMedGoogle Scholar
  66. 66.
    Raymond KN, Allred BE, Sia AK (2015) Coordination chemistry of microbial iron transport. Acc Chem Res 48:2496–2505. doi: 10.1021/acs.accounts.5b00301CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Wencewicz TA, Long TE, Möllmann U, Miller MJ (2013) Trihydroxamate siderophore-fluoroquinolone conjugates are selective sideromycin antibiotics that target Staphylococcus aureus. Bioconjug Chem 24:473–486. doi: 10.1021/bc300610fCrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Faraldo-Gomez JD, Sansom MS (2003) Acquisition of siderophores in Gram-negative bacteria. Nat Rev Mol Cell Biol 4:105–116. doi: 10.1038/nrm1015CrossRefPubMedGoogle Scholar
  69. 69.
    Troxell B, Hassan HM (2013) Transcriptional regulation by ferric uptake regulator (Fur) in pathogenic bacteria. Front Cell Infect Microbiol 3:59. doi: 10.3389/fcimb.2013.00059CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Hannauer M, Yeterian E, Martin LW, Lamont IL, Schalk IJ (2010) An efflux pump is involved in secretion of newly synthesized siderophore by Pseudomonas aeruginosa. FEBS Lett 584:4751–4755. doi: 10.1016/j.febslet.2010.10.051CrossRefPubMedGoogle Scholar
  71. 71.
    Hannauer M, Barda Y, Mislin GLA, Shanzer A, Schalk IJ (2010) The ferrichrome uptake pathway in Pseudomonas aeruginosa involves an iron release mechanism with acylation of the siderophore and recycling of the modified desferrichrome. J Bacteriol 192:1212–1220. doi: 10.1128/jb.01539-09CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Ferguson AD, Hofmann E, Coulton JW, Diederichs K, Welte W (1998) Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Science 282:2215–2220CrossRefGoogle Scholar
  73. 73.
    Celia H, Noinaj N, Zakharov SD, Bordignon E, Botos I, Santamaria M, Barnard TJ, Cramer WA, Lloubes R, Buchanan SK (2016) Structural insight into the role of the Ton complex in energy transduction. Nature 538:60–65. doi: 10.1038/nature19757CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Noinaj N, Guillier M, Barnard TJ, Buchanan SK (2010) TonB-dependent transporters: regulation, structure, and function. Annu Rev Microbiol 64:43–60. doi: 10.1146/annurev.micro.112408.134247CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Korkhov VM, Mireku SA, Locher KP (2012) Structure of AMP-PNP-bound vitamin B12 transporter BtuCD-F. Nature 490:367–372. doi: 10.1038/nature11442CrossRefPubMedGoogle Scholar
  76. 76.
    Schalk IJ, Guillon L (2013) Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathways. Amino Acids 44:1267–1277. doi: 10.1007/s00726-013-1468-2CrossRefPubMedGoogle Scholar
  77. 77.
    Li K, Chen W-H, Bruner SD (2015) Structure and mechanism of the siderophore-interacting protein from the fuscachelin gene cluster of Thermobifida fusca. Biochemistry 54:3989–4000. doi: 10.1021/acs.biochem.5b00354CrossRefPubMedGoogle Scholar
  78. 78.
    Lin H, Fischbach MA, Liu DR, Walsh CT (2005) In vitro characterization of salmochelin and enterobactin trilactone hydrolases IroD, IroE, and Fes. J Am Chem Soc 127:11075–11084. doi: 10.1021/ja0522027CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Frolow F, Kalb AJ, Yariv J (1994) Structure of a unique twofold symmetric haem-binding site. Nat Struct Biol 1:453–460. doi: 10.1038/nsb0794-453CrossRefPubMedGoogle Scholar
  80. 80.
    Sheldon JR, Heinrichs DE (2015) Recent developments in understanding the iron acquisition strategies of gram positive pathogens. FEMS Microbiol Rev 39:592–630. doi: 10.1093/femsre/fuv009CrossRefPubMedGoogle Scholar
  81. 81.
    Stintzi A, Barnes C, Xu J, Raymond KN (2000) Microbial iron transport via a siderophore shuttle: a membrane ion transport paradigm. Proc Natl Acad Sci U S A 97:10691–10696. doi: 10.1073/pnas.200318797CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Fukushima T, Allred BE, Sia AK, Nichiporuk R, Andersen UN, Raymond KN (2013) Gram-positive siderophore-shuttle with iron-exchange from Fe-siderophore to apo-siderophore by Bacillus cereus YxeB. Proc Natl Acad Sci U S A 110:13821–13826. doi: 10.1073/pnas.1304235110CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Fukushima T, Allred BE, Raymond KN (2014) Direct evidence of iron uptake by the Gram-positive siderophore-shuttle mechanism without iron reduction. ACS Chem Biol 9:2092–2100. doi: 10.1021/cb500319nCrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    D’Onofrio A, Crawford JM, Stewart EJ, Witt K, Gavrish E, Epstein S, Clardy J, Lewis K (2010) Siderophores from neighboring organisms promote the growth of uncultured bacteria. Chem Biol 17:254–264. doi: 10.1016/j.chembiol.2010.02.010CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Knusel F, Nuesch J (1965) Mechanism of action of sideromycins. Nature 206:674–676. doi: 10.1038/206674a0CrossRefPubMedGoogle Scholar
  86. 86.
    Pramanik A, Braun V (2006) Albomycin uptake via a ferric hydroxamate transport system of Streptococcus pneumoniae R6. J Bacteriol 188:3878–3886. doi: 10.1128/jb.00205-06CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Gause GF (1955) Recent studies on albomycin, a new antibiotic. BMJ 2:1177–1179. doi: 10.1136/bmj.2.4949.1177CrossRefPubMedGoogle Scholar
  88. 88.
    Zeng Y, Kulkarni A, Yang Z, Patil PB, Zhou W, Chi X, Van Lanen S, Chen S (2012) Biosynthesis of albomycin δ(2) provides a template for assembling siderophore and aminoacyl-tRNA synthetase inhibitor conjugates. ACS Chem Biol 7:1565–1575. doi: 10.1021/cb300173xCrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Kulkarni A, Zeng Y, Zhou W, Van Lanen S, Zhang W, Chen S (2015) A branch point of Streptomyces sulfur amino acid metabolism controls the production of albomycin. Appl Environ Microbiol 82:467–477. doi: 10.1128/aem.02517-15CrossRefPubMedGoogle Scholar
  90. 90.
    Stefanska AL, Fulston M, Houge-Frydrych CS, Jones JJ, Warr SR (2000) A potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species. J Antibiot 53:1346–1353. doi: 10.7164/antibiotics.53.1346CrossRefPubMedGoogle Scholar
  91. 91.
    Zeng Y, Roy H, Patil PB, Ibba M, Chen S (2009) Characterization of two seryl-tRNA synthetases in albomycin-producing Streptomyces sp. strain ATCC 700974. Antimicrob Agents Chemother 53:4619–4627. doi: 10.1128/aac.00782-09CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Ferguson AD, Braun V, Fiedler HP, Coulton JW, Diederichs K, Welte W (2000) Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA. Protein Sci 9:956–963. doi: 10.1110/ps.9.5.956CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Clarke TE, Braun V, Winkelmann G, Tari LW, Vogel HJ (2002) X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin. J Biol Chem 277:13966–13972. doi: 10.1074/jbc.M109385200CrossRefPubMedGoogle Scholar
  94. 94.
    Braun V, Gunthner K, Hantke K, Zimmermann L (1983) Intracellular activation of albomycin in Escherichia coli and Salmonella typhimurium. J Bacteriol 156:308–315PubMedPubMedCentralGoogle Scholar
  95. 95.
    Pramanik A, Stroeher UH, Krejci J, Standish AJ, Bohn E, Paton JC, Autenrieth IB, Braun V (2007) Albomycin is an effective antibiotic, as exemplified with Yersinia enterocolitica and Streptococcus pneumoniae. Int J Med Microbiol 297:459–469. doi: 10.1016/j.ijmm.2007.03.002CrossRefPubMedGoogle Scholar
  96. 96.
    Vértesy L, Aretz W, Fehlhaber H-W, Kogler H (1995) Salmycin A–D, antibiotika aus Streptomyces violaceus, DSM 8286, mit siderophor-aminoglycosid-struktur. Helv Chim Acta 78:46–60. doi: 10.1002/hlca.19950780105CrossRefGoogle Scholar
  97. 97.
    Huber P, Leuenberger H, Keller-Schierlein W (1986) Stoffwechselprodukte von mikroorganismen. 233. Mitteilung. Danoxamin, der eisenbindende teil des sideromycin-antibioticums danomycin. Helv Chim Acta 69:236–245. doi: 10.1002/hlca.19860690128CrossRefGoogle Scholar
  98. 98.
    Tsukiura H, Okanishi M, Ohmori T, Koshiyama H, Miyaki T, Kitazima H, Kawaguchi H (1964) Danomycin, a new antibiotic. J Antibiot 17:39–47PubMedGoogle Scholar
  99. 99.
    Wencewicz TA, Möllmann U, Long TE, Miller MJ (2009) Is drug release necessary for antimicrobial activity of siderophore-drug conjugates? Syntheses and biological studies of the naturally occurring salmycin “Trojan horse” antibiotics and synthetic desferridanoxamine-antibiotic conjugates. Biometals 22:633–648. doi: 10.1007/s10534-009-9218-3CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Bunet R, Brock A, Rexer HU, Takano E (2006) Identification of genes involved in siderophore transport in Streptomyces coelicolor A3(2). FEMS Microbiol Lett 262:57–64. doi: 10.1111/j.1574-6968.2006.00362.xCrossRefPubMedGoogle Scholar
  101. 101.
    Gwinner T (2008) Das siderophore-antibiotikum salmycin. Eberhard Karls Universitat Tübingen, TübingenGoogle Scholar
  102. 102.
    Mishra RP, Mariotti P, Fiaschi L, Nosari S, Maccari S, Liberatori S, Fontana MR, Pezzicoli A, De Falco MG, Falugi F, Altindis E, Serruto D, Grandi G, Bagnoli F (2012) Staphylococcus aureus FhuD2 is involved in the early phase of staphylococcal dissemination and generates protective immunity in mice. J Infect Dis 206:1041–1049. doi: 10.1093/infdis/jis463CrossRefPubMedGoogle Scholar
  103. 103.
    Arifin AJ, Hannauer M, Welch I, Heinrichs DE (2014) Deferoxamine mesylate enhances virulence of community-associated methicillin resistant Staphylococcus aureus. Microbes Infect 16:967–972. doi: 10.1016/j.micinf.2014.09.003CrossRefPubMedGoogle Scholar
  104. 104.
    Challis GL (2005) A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6:601–611. doi: 10.1002/cbic.200400283CrossRefPubMedGoogle Scholar
  105. 105.
    Roosenberg II JM, Miller MJ (2000) Total synthesis of the siderophore danoxamine. J Org Chem 65:4833–4838. doi: 10.1021/jo000050mCrossRefPubMedGoogle Scholar
  106. 106.
    Dong L, Roosenberg II JM, Miller MJ (2002) Total synthesis of desferrisalmycin B. J Am Chem Soc 124(50):15001–15005. doi: 10.1021/ja028386wCrossRefPubMedGoogle Scholar
  107. 107.
    Bachmann E, Zaehner H (1961) Metabolites of actinomycetes. 28. “In vitro” resistance to ferrimycin. Arch Mikrobiol 38:326–338CrossRefGoogle Scholar
  108. 108.
    Bickel H, Mertens P, Prelog V, Seibl J, Walser A (1965) Constitution of ferrimycin A1. Antimicrob Agents Chemother 5:951–957PubMedGoogle Scholar
  109. 109.
    Bickel H, Mertens P, Prelog V, Seibl J, Walser A (1966) Stoffwechselprodukte von mikroorganismen – 53: ueber die konstitution von ferrimycin A1. Tetrahedron 22:171–179. doi: 10.1016/S0040-4020(01)82182-7CrossRefGoogle Scholar
  110. 110.
    Urban A, Eckermann S, Fast B, Metzger S, Gehling M, Ziegelbauer K, Rübsamen-Waigmann H, Freiberg C (2007) Novel whole-cell antibiotic biosensors for compound discovery. Appl Environ Microbiol 73:6436–6443. doi: 10.1128/aem.00586-07CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Berner I, Winkelmann G (1990) Ferrioxamine transport mutants and the identification of the ferrioxamine receptor protein (FoxA) in Erwinia herbicola (Enterobacter agglomerans). Biol Met 2:197–202. doi: 10.1007/BF01141359CrossRefPubMedGoogle Scholar
  112. 112.
    Sackmann W, Reusser P, Neipp L, Kradolfer F, Gross F (1962) Ferrimycin A, a new iron-containing antibiotic. Antibiot Chemother 12:34–45Google Scholar
  113. 113.
    Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD, Craik DJ, Dawson M, Dittmann E, Donadio S, Dorrestein PC, Entian K-D, Fischbach MA, Garavelli JS, Goransson U, Gruber CW, Haft DH, Hemscheidt TK, Hertweck C, Hill C, Horswill AR, Jaspars M, Kelly WL, Klinman JP, Kuipers OP, Link AJ, Liu W, Marahiel MA, Mitchell DA, Moll GN, Moore BS, Muller R, Nair SK, Nes IF, Norris GE, Olivera BM, Onaka H, Patchett ML, Piel J, Reaney MJT, Rebuffat S, Ross RP, Sahl H-G, Schmidt EW, Selsted ME, Severinov K, Shen B, Sivonen K, Smith L, Stein T, Sussmuth RD, Tagg JR, Tang G-L, Truman AW, Vederas JC, Walsh CT, Walton JD, Wenzel SC, Willey JM, van der Donk WA (2013) Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 30:108–160. doi: 10.1039/C2NP20085FCrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Duquesne S, Destoumieux-Garzon D, Peduzzi J, Rebuffat S (2007) Microcins, gene-encoded antibacterial peptides from enterobacteria. Nat Prod Rep 24:708–734. doi: 10.1039/b516237hCrossRefPubMedGoogle Scholar
  115. 115.
    Thomas X, Destoumieux-Garzon D, Peduzzi J, Afonso C, Blond A, Birlirakis N, Goulard C, Dubost L, Thai R, Tabet JC, Rebuffat S (2004) Siderophore peptide, a new type of post-translationally modified antibacterial peptide with potent activity. J Biol Chem 279:28233–28242. doi: 10.1074/jbc.M400228200CrossRefPubMedGoogle Scholar
  116. 116.
    Nolan EM, Fischbach MA, Koglin A, Walsh CT (2007) Biosynthetic tailoring of microcin E492m: post-translational modification affords an antibacterial siderophore−peptide conjugate. J Am Chem Soc 129:14336–14347. doi: 10.1021/ja074650fCrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Nolan EM, Walsh CT (2008) Investigations of the MceIJ-catalyzed posttranslational modification of the microcin E492 C-terminus: linkage of ribosomal and nonribosomal peptides to form “Trojan horse” antibiotics. Biochemistry 47:9289–9299. doi: 10.1021/bi800826jCrossRefPubMedGoogle Scholar
  118. 118.
    Liu N, Shang F, Xi L, Huang Y (2013) Tetroazolemycins A and B, two new oxazole-thiazole siderophores from deep-sea Streptomyces olivaceus FXJ8.012. Mar Drugs 11:1524–1533. doi: 10.3390/md11051524CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Bachman MA, Oyler JE, Burns SH, Caza M, Lepine F, Dozois CM, Weiser JN (2011) Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect Immun 79:3309–3316. doi: 10.1128/iai.05114-11CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Brandel J, Humbert N, Elhabiri M, Schalk IJ, Mislin GLA, Albrecht-Gary A-M (2012) Pyochelin, a siderophore of Pseudomonas aeruginosa: physicochemical characterization of the iron(iii), copper(ii) and zinc(ii) complexes. Dalton Trans 41:2820–2834. doi: 10.1039/C1DT11804HCrossRefPubMedGoogle Scholar
  121. 121.
    Scharf DH, Heinekamp T, Remme N, Hortschansky P, Brakhage AA, Hertweck C (2012) Biosynthesis and function of gliotoxin in Aspergillus fumigatus. Appl Microbiol Biotechnol 93:467–472. doi: 10.1007/s00253-011-3689-1CrossRefPubMedGoogle Scholar
  122. 122.
    Zahner H, Diddens H, Keller-Schierlein W, Nageli HU (1977) Some experiments with semisynthetic sideromycins. Jpn J Antibiot 30:201–206PubMedGoogle Scholar
  123. 123.
    Page MG (2013) Siderophore conjugates. Ann N Y Acad Sci 1277:115–126. doi: 10.1111/nyas.12024CrossRefPubMedGoogle Scholar
  124. 124.
    Ji C, Juarez-Hernandez RE, Miller MJ (2012) Exploiting bacterial iron acquisition: siderophore conjugates. Future Med Chem 4:297–313. doi: 10.4155/fmc.11.191CrossRefPubMedGoogle Scholar
  125. 125.
    Górska A, Sloderbach A, Marszałł MP (2014) Siderophore–drug complexes: potential medicinal applications of the ‘Trojan horse’ strategy. Trends Pharmacol Sci 35:442–449. doi: 10.1016/j.tips.2014.06.007CrossRefPubMedGoogle Scholar
  126. 126.
    Mislin GL, Schalk IJ (2014) Siderophore-dependent iron uptake systems as gates for antibiotic Trojan horse strategies against Pseudomonas aeruginosa. Metallomics 6:408–420. doi: 10.1039/c3mt00359kCrossRefPubMedGoogle Scholar
  127. 127.
    Li K, Chen W-H, Bruner SD (2016) Microbial siderophore-based iron assimilation and therapeutic applications. Biometals 29:377–388. doi: 10.1007/s10534-016-9935-3CrossRefPubMedGoogle Scholar
  128. 128.
    Tillotson GS (2016) Trojan horse antibiotics – a novel way to circumvent gram-negative bacterial resistance? Infect Dis 9:45–52. doi: 10.4137/idrt.s31567CrossRefGoogle Scholar
  129. 129.
    Cherian PT, Deshpande A, Cheramie MN, Bruhn DF, Hurdle JG, Lee RE (2017) Design, synthesis and microbiological evaluation of ampicillin-tetramic acid hybrid antibiotics. J Antibiot 70:65–72. doi: 10.1038/ja.2016.52CrossRefPubMedGoogle Scholar
  130. 130.
    Starr J, Brown MF, Aschenbrenner L, Caspers N, Che Y, Gerstenberger BS, Huband M, Knafels JD, Lemmon MM, Li C, McCurdy SP, McElroy E, Rauckhorst MR, Tomaras AP, Young JA, Zaniewski RP, Shanmugasundaram V, Han S (2014) Siderophore receptor-mediated uptake of lactivicin analogues in Gram-negative bacteria. J Med Chem 57:3845–3855. doi: 10.1021/jm500219cCrossRefPubMedGoogle Scholar
  131. 131.
    Calvopiña K, Umland K-D, Rydzik AM, Hinchliffe P, Brem J, Spencer J, Schofield CJ, Avison MB (2016) Sideromimic modification of lactivicin dramatically increases potency against extensively drug-resistant Stenotrophomonas maltophilia clinical isolates. Antimicrob Agents Chemother 60:4170–4175. doi: 10.1128/aac.00371-16CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Poras H, Kunesch G, Barriere JC, Berthaud N, Andremont A (1998) Synthesis and in vitro antibacterial activity of catechol-spiramycin conjugates. J Antibiot 51:786–794. doi: 10.7164/antibiotics.51.786CrossRefPubMedGoogle Scholar
  133. 133.
    Ghosh M, Miller MJ (1995) Design, synthesis, and biological evaluation of isocyanurate-based antifungal and macrolide antibiotic conjugates: iron transport-mediated drug delivery. Bioorg Med Chem 3:1519–1525. doi: 10.1016/0968-0896(95)00134-3CrossRefPubMedGoogle Scholar
  134. 134.
    Alt S, Burkard N, Kulik A, Grond S, Heide L (2011) An artificial pathway to 3,4-dihydroxybenzoic acid allows generation of new aminocoumarin antibiotic recognized by catechol transporters of E. coli. Chem Biol 18:304–313. doi: 10.1016/j.chembiol.2010.12.016CrossRefPubMedGoogle Scholar
  135. 135.
    Bernier G, Girijavallabhan V, Murray A, Niyaz N, Ding P, Miller MJ, Malouin F (2005) Desketoneoenactin-siderophore conjugates for Candida: evidence of iron transport-dependent species selectivity. Antimicrob Agents Chemother 49:241–248. doi: 10.1128/aac.49.1.241-248.2005CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Lu Y, Miller MJ (1999) Syntheses and studies of multiwarhead siderophore-5-fluorouridine conjugates. Bioorg Med Chem 7:3025–3038. doi: 10.1016/S0968-0896(99)00248-5CrossRefPubMedGoogle Scholar
  137. 137.
    Wencewicz TA (2011) Development of microbe-selective antibacterial agents: From small molecules to siderophores. University of Notre Dame, Notre DameGoogle Scholar
  138. 138.
    Miller MJ, Walz AJ, Zhu H, Wu C, Moraski G, Mollmann U, Tristani EM, Crumbliss AL, Ferdig MT, Checkley L, Edwards RL, Boshoff HI (2011) Design, synthesis, and study of a mycobactin-artemisinin conjugate that has selective and potent activity against tuberculosis and malaria. J Am Chem Soc 133:2076–2079. doi: 10.1021/ja109665tCrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Ramurthy S, Miller MJ (1996) Framework-reactive siderophore analogs as potential cell-selective drugs. Design and syntheses of trimelamol-based iron chelators. J Org Chem 61:4120–4124. doi: 10.1021/jo9600621CrossRefPubMedGoogle Scholar
  140. 140.
    Juárez-Hernández RE, Miller PA, Miller MJ (2012) Syntheses of siderophore–drug conjugates using a convergent thiol–maleimide system. ACS Med Chem Lett 3:799–803. doi: 10.1021/ml300150yCrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Ghosh M, Miller MJ (1996) Synthesis and in vitro antibacterial activity of spermidine-based mixed catechol- and hydroxamate-containing siderophore–vancomycin conjugates. Bioorg Med Chem 4:43–48. doi: 10.1016/0968-0896(95)00161-1CrossRefPubMedGoogle Scholar
  142. 142.
    Yoganathan S, Sit CS, Vederas JC (2011) Chemical synthesis and biological evaluation of gallidermin-siderophore conjugates. Org Biomol Chem 9:2133–2141. doi: 10.1039/c0ob00846jCrossRefPubMedGoogle Scholar
  143. 143.
    Ghosh M, Miller PA, Möllmann U, Claypool WD, Schroeder VA, Wolter WR, Suckow M, Yu H, Li S, Huang W, Zajicek J, Miller MJ (2017) Targeted antibiotic delivery: selective siderophore conjugation with daptomycin confers potent activity against multidrug resistant Acinetobacter baumannii both in vitro and in vivo. J Med Chem. doi: 10.1021/acs.jmedchem.7b00102 (Epub ahead of print)
  144. 144.
    McPherson CJ, Aschenbrenner LM, Lacey BM, Fahnoe KC, Lemmon MM, Finegan SM, Tadakamalla B, O’Donnell JP, Mueller JP, Tomaras AP (2012) Clinically relevant Gram-negative resistance mechanisms have no effect on the efficacy of MC-1, a novel siderophore-conjugated monocarbam. Antimicrob Agents Chemother 56:6334–6342. doi: 10.1128/aac.01345-12CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Barbachyn MR, Tuominen TC (1990) Synthesis and structure-activity relationships of monocarbams leading to U-78608. J Antibiot 43:1199–1203. doi: 10.7164/antibiotics.43.1199CrossRefPubMedGoogle Scholar
  146. 146.
    Higgins PG, Stefanik D, Page MG, Hackel M, Seifert H (2012) In vitro activity of the siderophore monosulfactam BAL30072 against meropenem-non-susceptible Acinetobacter baumannii. J Antimicrob Chemother 67:1167–1169. doi: 10.1093/jac/dks009CrossRefPubMedGoogle Scholar
  147. 147.
    Hofer B, Dantier C, Gebhardt K, Desarbre E, Schmitt-Hoffmann A, Page MG (2013) Combined effects of the siderophore monosulfactam BAL30072 and carbapenems on multidrug-resistant Gram-negative bacilli. J Antimicrob Chemother 68:1120–1129. doi: 10.1093/jac/dks527CrossRefPubMedGoogle Scholar
  148. 148.
    Hornsey M, Phee L, Stubbings W, Wareham DW (2013) In vitro activity of the novel monosulfactam BAL30072 alone and in combination with meropenem versus a diverse collection of important Gram-negative pathogens. Int J Antimicrob Agents 42:343–346. doi: 10.1016/j.ijantimicag.2013.05.010CrossRefPubMedGoogle Scholar
  149. 149.
    Landman D, Singh M, El-Imad B, Miller E, Win T, Quale J (2014) In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City, including multidrug-resistant isolates. Int J Antimicrob Agents 43:527–532. doi: 10.1016/j.ijantimicag.2014.02.017CrossRefPubMedGoogle Scholar
  150. 150.
    Mushtaq S, Warner M, Livermore D (2010) Activity of the siderophore monobactam BAL30072 against multiresistant non-fermenters. J Antimicrob Chemother 65:266–270. doi: 10.1093/jac/dkp425CrossRefPubMedGoogle Scholar
  151. 151.
    Page MG, Dantier C, Desarbre E (2010) In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant gram-negative bacilli. Antimicrob Agents Chemother 54:2291–2302. doi: 10.1128/aac.01525-09CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Russo TA, Page MG, Beanan JM, Olson R, Hujer AM, Hujer KM, Jacobs M, Bajaksouzian S, Endimiani A, Bonomo RA (2011) In vivo and in vitro activity of the siderophore monosulfactam BAL30072 against Acinetobacter baumannii. J Antimicrob Chemother 66:867–873. doi: 10.1093/jac/dkr013CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    van Delden C, Page MG, Kohler T (2013) Involvement of Fe uptake systems and AmpC beta-lactamase in susceptibility to the siderophore monosulfactam BAL30072 in Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:2095–2102. doi: 10.1128/aac.02474-12CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    Tomaras AP, Crandon JL, McPherson CJ, Banevicius MA, Finegan SM, Irvine RL, Brown MF, O’Donnell JP, Nicolau DP (2013) Adaptation-based resistance to siderophore-conjugated antibacterial agents by Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:4197–4207. doi: 10.1128/aac.00629-13CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Han S, Zaniewski RP, Marr ES, Lacey BM, Tomaras AP, Evdokimov A, Miller JR, Shanmugasundaram V (2010) Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 107:22002–22007. doi: 10.1073/pnas.1013092107CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Flanagan ME, Brickner SJ, Lall M, Casavant J, Deschenes L, Finegan SM, George DM, Granskog K, Hardink JR, Huband MD, Hoang T, Lamb L, Marra A, Mitton-Fry M, Mueller JP, Mullins LM, Noe MC, O’Donnell JP, Pattavina D, Penzien JB, Schuff BP, Sun J, Whipple DA, Young J, Gootz TD (2011) Preparation, Gram-negative antibacterial activity, and hydrolytic stability of novel siderophore-conjugated monocarbam diols. ACS Med Chem Lett 2:385–390. doi: 10.1021/ml200012fCrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    Ito A, Nishikawa T, Matsumoto S, Yoshizawa H, Sato T, Nakamura R, Tsuji M, Yamano Y (2016) Siderophore cephalosporin cefiderocol utilizes ferric iron transporter systems for antibacterial activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother 60:7396–7401. doi: 10.1128/aac.01405-16CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Ito A, Kohira N, Bouchillon SK, West J, Rittenhouse S, Sader HS, Rhomberg PR, Jones RN, Yoshizawa H, Nakamura R, Tsuji M, Yamano Y (2016) In vitro antimicrobial activity of S-649266, a catechol-substituted siderophore cephalosporin, when tested against non-fermenting Gram-negative bacteria. J Antimicrob Chemother 71:670–677. doi: 10.1093/jac/dkv402CrossRefPubMedGoogle Scholar
  159. 159.
    Kohira N, West J, Ito A, Ito-Horiyama T, Nakamura R, Sato T, Rittenhouse S, Tsuji M, Yamano Y (2016) In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother 60:729–734. doi: 10.1128/aac.01695-15CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Möllmann U, Heinisch L, Bauernfeind A, Kohler T, Ankel-Fuchs D (2009) Siderophores as drug delivery agents: application of the “Trojan horse” strategy. Biometals 22:615–624. doi: 10.1007/s10534-009-9219-2CrossRefPubMedGoogle Scholar
  161. 161.
    Kline T, Fromhold M, McKennon TE, Cai S, Treiberg J, Ihle N, Sherman D, Schwan W, Hickey MJ, Warrener P, Witte PR, Brody LL, Goltry L, Barker LM, Anderson SU, Tanaka SK, Shawar RM, Nguyen LY, Langhorne M, Bigelow A, Embuscado L, Naeemi E (2000) Antimicrobial effects of novel siderophores linked to β-lactam antibiotics. Bioorg Med Chem 8:73–93. doi: 10.1016/S0968-0896(99)00261-8CrossRefPubMedGoogle Scholar
  162. 162.
    Kim A, Kutschke A, Ehmann DE, Patey SA, Crandon JL, Gorseth E, Miller AA, McLaughlin RE, Blinn CM, Chen A, Nayar AS, Dangel B, Tsai AS, Rooney MT, Murphy-Benenato KE, Eakin AE, Nicolau DP (2015) Pharmacodynamic profiling of a siderophore-conjugated monocarbam in Pseudomonas aeruginosa: assessing the risk for resistance and attenuated efficacy. Antimicrob Agents Chemother 59:7743–7752. doi: 10.1128/aac.00831-15CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Minnick AA, McKee JA, Dolence EK, Miller MJ (1992) Iron transport-mediated antibacterial activity of and development of resistance to hydroxamate and catechol siderophore-carbacepholosporin conjugates. Antimicrob Agents Chemother 36:840–850. doi: 10.1128/AAC.36.4.840CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    Diarra MS, Lavoie MC, Jacques M, Darwish I, Dolence EK, Dolence JA, Ghosh A, Ghosh M, Miller MJ, Malouin F (1996) Species selectivity of new siderophore-drug conjugates that use specific iron uptake for entry into bacteria. Antimicrob Agents Chemother 40:2610–2617PubMedPubMedCentralGoogle Scholar
  165. 165.
    Ghosh A, Ghosh M, Niu C, Malouin F, Möllmann U, Miller MJ (1996) Iron transport-mediated drug delivery using mixed-ligand siderophore-β-lactam conjugates. Chem Biol 3(12):1011–1019. doi: 10.1016/S1074-5521(96)90167-2CrossRefPubMedGoogle Scholar
  166. 166.
    Wencewicz TA, Miller MJ (2013) Biscatecholate-monohydroxamate mixed ligand siderophore-carbacephalosporin conjugates are selective sideromycin antibiotics that target Acinetobacter baumannii. J Med Chem 56:4044–4052. doi: 10.1021/jm400265kCrossRefPubMedPubMedCentralGoogle Scholar
  167. 167.
    Proschak A, Lubuta P, Grun P, Lohr F, Wilharm G, De Berardinis V, Bode HB (2013) Structure and biosynthesis of fimsbactins A-F, siderophores from Acinetobacter baumannii and Acinetobacter baylyi. ChemBioChem 14:633–638. doi: 10.1002/cbic.201200764CrossRefPubMedGoogle Scholar
  168. 168.
    Rivault F, Liebert C, Burger A, Hoegy F, Abdallah MA, Schalk IJ, Mislin GL (2007) Synthesis of pyochelin-norfloxacin conjugates. Bioorg Med Chem Lett 17:640–644. doi: 10.1016/j.bmcl.2006.11.005CrossRefPubMedGoogle Scholar
  169. 169.
    Milner SJ, Seve A, Snelling AM, Thomas GH, Kerr KG, Routledge A, Duhme-Klair AK (2013) Staphyloferrin A as siderophore-component in fluoroquinolone-based Trojan horse antibiotics. Org Biomol Chem 11:3461–3468. doi: 10.1039/c3ob40162fCrossRefPubMedGoogle Scholar
  170. 170.
    Souto A, Montaos MA, Balado M, Osorio CR, Rodriguez J, Lemos ML, Jimenez C (2013) Synthesis and antibacterial activity of conjugates between norfloxacin and analogues of the siderophore vanchrobactin. Bioorg Med Chem 21:295–302. doi: 10.1016/j.bmc.2012.10.028CrossRefPubMedGoogle Scholar
  171. 171.
    Kinzel O, Tappe R, Gerus I, Budzikiewicz H (1998) The synthesis and antibacterial activity of two pyoverdin-ampicillin conjugates, entering Pseudomonas aeruginosa via the pyoverdin-mediated iron uptake pathway. J Antibiot 51:499–507. doi: 10.7164/antibiotics.51.499CrossRefPubMedGoogle Scholar
  172. 172.
    Zheng T, Nolan EM (2014) Enterobactin-mediated delivery of β-lactam antibiotics enhances antibacterial activity against pathogenic Escherichia coli. J Am Chem Soc 136:9677–9691. doi: 10.1021/ja503911pCrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    Chairatana P, Zheng T, Nolan EM (2015) Targeting virulence: salmochelin modification tunes the antibacterial activity spectrum of β-lactams for pathogen-selective killing of Escherichia coli. Chem Sci 6:4458–4471. doi: 10.1039/C5SC00962FCrossRefPubMedPubMedCentralGoogle Scholar
  174. 174.
    Jarrad AM, Karoli T, Blaskovich MAT, Lyras D, Cooper MA (2015) Clostridium difficile drug pipeline: challenges in discovery and development of new agents. J Med Chem 58:5164–5185. doi: 10.1021/jm5016846CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    Shapiro J, Wencewicz TA (2017) Structure-function studies of acinetobactin analogs. Metallomics. doi: 10.1039/c7mt00064bCrossRefPubMedGoogle Scholar
  176. 176.
    Kinzel O, Budzikiewicz H (1999) Synthesis and biological evaluation of a pyoverdin-β-lactam conjugate: a new type of arginine-specific cross-linking in aqueous solution. J Pept Res 53:618–625. doi: 10.1034/j.1399-3011.1999.00053.xCrossRefPubMedGoogle Scholar
  177. 177.
    Hennard C, Truong QC, Desnottes JF, Paris JM, Moreau NJ, Abdallah MA (2001) Synthesis and activities of pyoverdin-quinolone adducts: a prospective approach to a specific therapy against Pseudomonas aeruginosa. J Med Chem 44:2139–2151. doi: 10.1021/jm990508gCrossRefPubMedGoogle Scholar
  178. 178.
    Ganne G, Brillet K, Basta B, Roche B, Hoegy F, Gasser V, Schalk IJ (2017) Iron release from the siderophore pyoverdine in Pseudomonas aeruginosa involves three new actors: FpvC, FpvG, and FpvH. ACS Chem Biol. doi: 10.1021/acschembio.6b01077 (Epub ahead of print)
  179. 179.
    Zheng T, Nolan EM (2015) Evaluation of (acyloxy)alkyl ester linkers for antibiotic release from siderophore–antibiotic conjugates. Bioorg Med Chem Lett 25:4987–4991. doi: 10.1016/j.bmcl.2015.02.034CrossRefPubMedGoogle Scholar
  180. 180.
    Ji C, Miller MJ (2012) Chemical syntheses and in vitro antibacterial activity of two desferrioxamine B-ciprofloxacin conjugates with potential esterase and phosphatase triggered drug release linkers. Bioorg Med Chem 20:3828–3836. doi: 10.1016/j.bmc.2012.04.034CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Ji C, Miller MJ (2015) Siderophore–fluoroquinolone conjugates containing potential reduction-triggered linkers for drug release: synthesis and antibacterial activity. Biometals 28:541–551. doi: 10.1007/s10534-015-9830-3CrossRefPubMedPubMedCentralGoogle Scholar
  182. 182.
    Gootenberg JS, Abudayyeh OO, Lee JW, Essletzbichler P, Day AJ, Joung J, Verdine V, Donghia N, Daringer NM, Freije CA, Myhrvold C, Bhattacharyya RP, Livny J, Regev A, Koonin EV, Hung DT, Sabeti PC, Collins JJ, Zhang F (2017) Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. doi: 10.1126/science.aam9321 (Epub ahead of print)
  183. 183.
    Doorneweerd DD, Henne WA, Reifenberger RG, Low PS (2010) Selective capture and identification of pathogenic bacteria using an immobilized siderophore. Langmuir 26:15424–15429. doi: 10.1021/la101962wCrossRefPubMedGoogle Scholar
  184. 184.
    Wolfenden M, Sakamuri R, Anderson A, Prasad L, Schmidt J, Mukundan H (2012) Determination of bacterial viability by selective capture using surface-bound siderophores. Adv Biol Chem 2:396–402. doi: 10.4236/abc.2012.24049CrossRefGoogle Scholar
  185. 185.
    Zheng T, Nolan EM (2012) Siderophore-based detection of Fe(iii) and microbial pathogens. Metallomics 4:866–880. doi: 10.1039/C2MT20082ACrossRefPubMedGoogle Scholar
  186. 186.
    Pahlow S, Stöckel S, Pollok S, Cialla-May D, Rösch P, Weber K, Popp J (2016) Rapid identification of Pseudomonas spp. via Raman spectroscopy using pyoverdine as capture probe. Anal Chem 88:1570–1577. doi: 10.1021/acs.analchem.5b02829CrossRefPubMedGoogle Scholar
  187. 187.
    Kurth C, Kage H, Nett M (2016) Siderophores as molecular tools in medical and environmental applications. Org Biomol Chem 14:8212–8227. doi: 10.1039/C6OB01400CCrossRefPubMedGoogle Scholar
  188. 188.
    Johnstone TC, Nolan EM (2015) Beyond iron: non-classical biological functions of bacterial siderophores. Dalton Trans 44:6320–6339. doi: 10.1039/c4dt03559cCrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of ChemistryWashington University in St. LouisSt. LouisUSA
  2. 2.Department of Chemistry and BiochemistryUniversity of Notre DameNotre DameUSA

Personalised recommendations