Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron

References

• Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124:3–20; quiz 1–2. doi:10.1016/j.jaci.2009.05.038.
   PubMed Web of Science ®Google Scholar
• Okumura R, Takeda K. Roles of intestinal epithelial cells in the maintenance of gut homeostasis. Exp Mol Med. 2017;49:e338. doi:10.1038/emm.2017.20.
   PubMed Web of Science ®Google Scholar
• Yu Y, Zeng H, Lyons S, Carlson A, Merlin D, Neish AS, Gewirtz AT. TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism. Am J Physiol Gastrointest Liver Physiol. 2003;285(2):G282–90. doi:10.1152/ajpgi.00503.2002.
   PubMed Web of Science ®Google Scholar
• Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol. 2001;167:1882–1885. doi:10.4049/jimmunol.167.4.1882.
   PubMed Web of Science ®Google Scholar
• Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;91:151–175.
   PubMed Web of Science ®Google Scholar
• Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011;474:298–306. doi:10.1038/nature10208.
   PubMed Web of Science ®Google Scholar
• Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–1772. doi:10.2337/db06-1491.
   PubMed Web of Science ®Google Scholar
• Liang S, Guo XK, Ou J, Huang R, Xue Q, Zhang B, Yeonseok Chung Y, Wu W, Dong C, Yang X, Hu X. Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1. Cell Host Microbe. 2019;25:706–18e7.
   PubMed Web of Science ®Google Scholar
• Borregaard N, Cowland JB. Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein. Biometals. 2006;19(2):211–215. doi:10.1007/s10534-005-3251-7.
   PubMed Web of Science ®Google Scholar
• Ratledge C, Dover LG. Iron metabolism in pathogenic bacteria. Annu Rev Microbiol. 2000;54:881–941. doi:10.1146/annurev.micro.54.1.881.
   PubMed Web of Science ®Google Scholar
• Abergel RJ, Warner JA, Shuh DK, Raymond KN. Enterobactin protonation and iron release: structural characterization of the salicylate coordination shift in ferric enterobactin. J Am Chem Soc. 2006;128:8920–8931. doi:10.1021/ja062046j.
   PubMed Web of Science ®Google Scholar
• Fischbach MA, Lin H, Liu DR, Walsh CT. How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat Chem Biol. 2006;2:132–138. doi:10.1038/nchembio771.
   PubMed Web of Science ®Google Scholar
• 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. 2006;1:29–32. doi:10.1021/cb0500034.
   PubMed Web of Science ®Google Scholar
• Saha P, Yeoh BS, Xiao X, Golonka RM, Kumarasamy S, Vijay-Kumar M. Enterobactin, an iron chelating bacterial siderophore, arrests cancer cell proliferation. Biochem Pharmacol. 2019;168:71–81. doi:10.1016/j.bcp.2019.06.017.
   PubMed Web of Science ®Google Scholar
• Saha P, Xiao X, Yeoh BS, Chen Q, Katkere B, Kirimanjeswara GS, Vijay-Kumar M. The bacterial siderophore enterobactin confers survival advantage to Salmonella in macrophages. Gut Microbes. 2019;10:412–423. doi:10.1080/19490976.2018.1546519.
   PubMed Web of Science ®Google Scholar
• Saha P, Yeoh BS, Olvera RA, Xiao X, Singh V, Awasthi D, Subramanian BC, Chen Q, Dikshit M, Wang Y. Bacterial siderophores hijack neutrophil functions. The Journal of Immunology. 2017;198(11):4293–4303. doi:10.4049/jimmunol.1700261.
   PubMed Web of Science ®Google Scholar
• Pi H, Jones SA, Mercer LE, Meador JP, Caughron JE, Jordan L, Newton SM, Conway T, Klebba PE. Role of catecholate siderophores in gram-negative bacterial colonization of the mouse gut. PLoS One. 2012;7(11):e50020. doi:10.1371/journal.pone.0050020.
   PubMed Web of Science ®Google Scholar
• May T, Okabe S. Enterobactin is required for biofilm development in reduced-genome Escherichia coli. Environ Microbiol. 2011;13(12):3149–3162. doi:10.1111/j.1462-2920.2011.02607.x.
   PubMed Web of Science ®Google Scholar
• Peralta DR, Adler C, Corbalan NS, Paz Garcia EC, Pomares MF, Vincent PA. Enterobactin as part of the oxidative stress response repertoire. PloS One. 2016;11:e0157799. doi:10.1371/journal.pone.0157799.
   PubMed Web of Science ®Google Scholar
• Adler C, Corbalan NS, Peralta DR, Pomares MF, de Cristobal RE, Vincent PA. The alternative role of enterobactin as an oxidative stress protector allows Escherichia coli colony development. PloS One. 2014;9:e84734. doi:10.1371/journal.pone.0084734.
   PubMed Web of Science ®Google Scholar
• Achard ME, Chen KW, Sweet MJ, Watts RE, Schroder K, Schembri MA, McEwan A. An antioxidant role for catecholate siderophores in Salmonella. Biochem J. 2013;454:543–549. doi:10.1042/BJ20121771.
   PubMed Web of Science ®Google Scholar
• Coker MS, Forbes LV, Plowman-Holmes M, Murdoch DR, Winterbourn CC, Kettle AJ. Interactions of staphyloxanthin and enterobactin with myeloperoxidase and reactive chlorine species. Arch Biochem Biophys. 2018;646:80–89. doi:10.1016/j.abb.2018.03.039.
   PubMed Web of Science ®Google Scholar
• Singh V, Yeoh BS, Xiao X, Kumar M, Bachman M, Borregaard N, Joe B, Vijay-Kumar M. Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut. Nat Commun. 2015;6(1):7113. doi:10.1038/ncomms8113.
   PubMedGoogle Scholar
• Valdebenito M, Muller SI, Hantke K. Special conditions allow binding of the siderophore salmochelin to siderocalin (NGAL-lipocalin). FEMS Microbiol Lett. 2007;277:182–187. doi:10.1111/j.1574-6968.2007.00956.x.
   PubMed Web of Science ®Google Scholar
• Coorens M, Rao A, Grafe SK, Unelius D, Lindforss U, Agerberth B, Mjösberg J, Bergman P. Innate lymphoid cell type 3-derived interleukin-22 boosts lipocalin-2 production in intestinal epithelial cells via synergy between STAT3 and NF-kappaB. J Biol Chem. 2019;294:6027–6041. doi:10.1074/jbc.RA118.007290.
   PubMed Web of Science ®Google Scholar
• Wu H, Santoni-Rugiu E, Ralfkiaer E, Porse BT, Moser C, Hoiby N, Borregaard N, Cowland JB. Lipocalin 2 is protective against E. coli pneumonia. Respir Res. 2010;11(1):96. doi:10.1186/1465-9921-11-96.
   PubMedGoogle Scholar
• Nelson AL, Ratner AJ, Barasch J, Weiser JN. Interleukin-8 secretion in response to aferric enterobactin is potentiated by siderocalin. Infect Immun. 2007;75:3160–3168. doi:10.1128/IAI.01719-06.
   PubMed Web of Science ®Google Scholar
• Holden VI, Lenio S, Kuick R, Ramakrishnan SK, Shah YM, Bachman MA. Bacterial siderophores that evade or overwhelm lipocalin 2 induce hypoxia inducible factor 1alpha and proinflammatory cytokine secretion in cultured respiratory epithelial cells. Infect Immun. 2014;82:3826–3836. doi:10.1128/IAI.01849-14.
   PubMed Web of Science ®Google Scholar
• Golonka R, Yeoh BS, Vijay-Kumar M. The Iron Tug-of-War between Bacterial Siderophores and Innate Immunity. J Innate Immun. 2019;11:249–262.
   PubMed Web of Science ®Google Scholar
• Xiao X, Yeoh BS, Saha P, Tian Y, Singh V, Patterson AD, Vijay-Kumar M. Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice. J Nutr Biochem. 2017;41:25–33.
   PubMed Web of Science ®Google Scholar
• Kakhlon O, Cabantchik ZI. The labile iron pool: characterization, measurement, and participation in cellular processes(1). Free Radic Biol Med. 2002;33:1037–1046. doi:10.1016/S0891-5849(02)01006-7.
   PubMed Web of Science ®Google Scholar
• Cabantchik ZI, Glickstein H, Milgram P, Breuer W. A fluorescence assay for assessing chelation of intracellular iron in a membrane model system and in mammalian cells. Anal Biochem. 1996;233:221–227. doi:10.1006/abio.1996.0032.
   PubMed Web of Science ®Google Scholar
• Glickstein H, El RB, Shvartsman M, Cabantchik ZI. Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood. 2005;106:3242–3250. doi:10.1182/blood-2005-02-0460.
   PubMed Web of Science ®Google Scholar
• Chan FK, Moriwaki K, De Rosa MJ. Detection of necrosis by release of lactate dehydrogenase activity. Methods Mole Biol. 2013;979:65–70.
   PubMedGoogle Scholar
• Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem. 1998;67:227–264. doi:10.1146/annurev.biochem.67.1.227.
   PubMed Web of Science ®Google Scholar
• Miethke M, Marahiel MA. Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev. 2007;71:413–451.
   PubMed Web of Science ®Google Scholar
• Raymond KN, Dertz EA, Kim SS. Enterobactin: an archetype for microbial iron transport. Proc Natl Acad Sci U S A. 2003;100:3584–3588.
   PubMed Web of Science ®Google Scholar
• Richardson DR, Hefter GT, May PM, Webb J, Baker E. Iron chelators of the pyridoxal isonicotinoyl hydrazone class. III. Formation constants with calcium(II), magnesium(II) and zinc(II). Biol Met. 1989;2:161–167. doi:10.1007/BF01142555.
   PubMedGoogle Scholar
• Goodwin JF, Whitten CF. Chelation of ferrous sulphate solutions by desferrioxamine B. Nature. 1965;205:281–283. doi:10.1038/205281b0.
   PubMed Web of Science ®Google Scholar
• Loomis LD, Raymond KN. Solution equilibria of enterobactin and metal-enterobactin complexes. Inorg Chem. 1991;30:906–911. doi:10.1021/ic00005a008.
   Web of Science ®Google Scholar
• Choi EY, Park ZY, Choi EJ, Oh HM, Lee S, Choi SC, Lee KM, Im SH, Chun JS, Jun CD. Transcriptional regulation of IL-8 by iron chelator in human epithelial cells is independent from NF-kappaB but involves ERK1/2- and p38 kinase-dependent activation of AP-1. J Cell Biochem. 2007;102:1442–1457.
   PubMed Web of Science ®Google Scholar
• Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, Yoon KH, Kim EA, Han WC, Choi SC, et al. Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways. J Immunol. 2004;172:7069–7077.
   PubMed Web of Science ®Google Scholar
• Alam A, Leoni G, Wentworth CC, Kwal JM, Wu H, Ardita CS, Swanson PA, Lambeth JD, Jones RM, Nusrat A. Redox signaling regulates commensal-mediated mucosal homeostasis and restitution and requires formyl peptide receptor 1. Mucosal Immunol. 2014;7(3):645–655. doi:10.1038/mi.2013.84.
   PubMed Web of Science ®Google Scholar
• Moll F, Walter M, Rezende F, Helfinger V, Vasconez E, De Oliveira T, Greten FR, Olesch C, Weigert A, Radeke HH. NoxO1 Controls Proliferation of Colon Epithelial Cells. Front Immunol. 2018;9:973. doi:10.3389/fimmu.2018.00973.
   PubMed Web of Science ®Google Scholar
• Nakamura T, Naguro I, Ichijo H. Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases. Biochim Biophys Acta Gen Subj. 2019;1863(9):1398–1409. doi:10.1016/j.bbagen.2019.06.010.
   PubMed Web of Science ®Google Scholar
• Babbin BA, Jesaitis AJ, Ivanov AI, Kelly D, Laukoetter M, Nava P, Parkos CA, Nusrat A. Formyl peptide receptor-1 activation enhances intestinal epithelial cell restitution through phosphatidylinositol 3-kinase-dependent activation of Rac1 and Cdc42. J Immunol. 2007;179(12):8112–8121. doi:10.4049/jimmunol.179.12.8112.
   PubMed Web of Science ®Google Scholar
• Leslie AD, Daneshfar R, Volmer DA. Infrared multiphoton dissociation of the siderophore enterobactin and its Fe(III) complex. Influence of Fe(III) binding on dissociation kinetics and relative energetics. J Am Soc Mass Spectrom. 2007;18(4):632–641. doi:10.1016/j.jasms.2006.11.011.
   PubMed Web of Science ®Google Scholar
• Nawaz IM, Chiodelli P, Rezzola S, Paganini G, Corsini M, Lodola A, Di Ianni A, Mor M, Presta M. N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors. Angiogenesis. 2018;21(1):47–59. doi:10.1007/s10456-017-9581-6.
   PubMed Web of Science ®Google Scholar
• McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and mineral nutrition information system, 1993-2005. Public Health Nutr. 2009;12:444–454.
   PubMed Web of Science ®Google Scholar
• Qi B, Han M. Microbial siderophore enterobactin promotes mitochondrial iron uptake and development of the host via interaction with ATP synthase. Cell. 2018;175(2):571–82e11. doi:10.1016/j.cell.2018.07.032.
   PubMed Web of Science ®Google Scholar
• Xiao X, Yeoh BS, Vijay-Kumar M. Lipocalin 2: an emerging player in iron homeostasis and inflammation. Annu Rev Nutr. 2017;37(1):103–130. doi:10.1146/annurev-nutr-071816-064559.
   PubMed Web of Science ®Google Scholar
• Gewirtz AT, Simon PO Jr., Schmitt CK, Taylor LJ, Hagedorn CH, O’Brien AD, Neish AS, Madara JL. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J Clin Invest. 2001;107:99–109. doi:10.1172/JCI10501.
   PubMed Web of Science ®Google Scholar
• Holden VI, Breen P, Houle S, Dozois CM, Bachman MA. Klebsiella pneumoniae siderophores induce inflammation, bacterial dissemination, and HIF-1alpha stabilization during pneumonia. mBio. 2016;7. doi:10.1128/mBio.01397-16.
   Web of Science ®Google Scholar
• Bachman MA, Miller VL, Weiser JN. Mucosal lipocalin 2 has pro-inflammatory and iron-sequestering effects in response to bacterial enterobactin. PLoS Pathog. 2009;5:e1000622. doi:10.1371/journal.ppat.1000622.
   PubMed Web of Science ®Google Scholar
• Casey JL, Hentze MW, Koeller DM, Caughman SW, Rouault TA, Klausner RD, Harford J. Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. Science. 1988;240:924–928. doi:10.1126/science.2452485.
   PubMed Web of Science ®Google Scholar
• Tenopoulou M, Kurz T, Doulias PT, Galaris D, Brunk UT. Does the calcein-AM method assay the total cellular ‘labile iron pool’ or only a fraction of it? Biochem J. 2007;403:261–266. doi:10.1042/BJ20061840.
   PubMed Web of Science ®Google Scholar
• 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. 2002;10:1033–1043. doi:10.1016/S1097-2765(02)00708-6.
   PubMed Web of Science ®Google Scholar
• Sun J, Fegan PE, Desai AS, Madara JL, Hobert ME. Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2007;292:G767–78. doi:10.1152/ajpgi.00447.2006.
   PubMed Web of Science ®Google Scholar
• Alta RY, Vitorino HA, Goswami D, Liria CW, Wisnovsky SP, Kelley SO, Machini MT, Espósito BP. Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron. PLoS One. 2017;12:e0171729. doi:10.1371/journal.pone.0171729.
   PubMed Web of Science ®Google Scholar
• Chen K, Liu M, Liu Y, Yoshimura T, Shen W, Le Y, Durum S, Gong W, Wang C, Gao J-L. Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis. J Clin Invest. 2013;123(4):1694–1704. doi:10.1172/JCI65569.
   PubMed Web of Science ®Google Scholar
• Warner N, Nunez G. MyD88: a critical adaptor protein in innate immunity signal transduction. J Immunol. 2013;190(1):3–4. doi:10.4049/jimmunol.1203103.
   PubMed Web of Science ®Google Scholar
• Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146:1489–1499. doi:10.1053/j.gastro.2014.02.009.
   PubMed Web of Science ®Google Scholar
• Payne SM. Iron and virulence in the family Enterobacteriaceae. Crit Rev Microbiol. 1988;16:81–111. doi:10.3109/10408418809104468.
   PubMed Web of Science ®Google Scholar
• Wenceslau CF, McCarthy CG, Szasz T, Calmasini FB, Mamenko M, Webb RC. Formyl peptide receptor-1 activation exerts a critical role for the dynamic plasticity of arteries via actin polymerization. Pharmacol Res. 2019;141:276–290. doi:10.1016/j.phrs.2019.01.015.
   PubMed Web of Science ®Google Scholar
• Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004;432(7019):917–921. doi:10.1038/nature03104.
   PubMed Web of Science ®Google Scholar
• Kjeldsen L, Cowland JB, Borregaard N. Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse. Biochim Biophys Acta. 2000;1482:272–283.
   PubMed Web of Science ®Google Scholar
• Schwyn B, Neilands JB. Universal chemical assay for the detection and determination of siderophores. Anal Biochem. 1987;160:47–56. doi:10.1016/0003-2697(87)90612-9.
   PubMed Web of Science ®Google Scholar
• Saha P, Xiao X, Yeoh BS, Chen Q, Katkere B, Kirimanjeswara GS, et alVijay-Kumar M. The bacterial siderophore enterobactin confers survival advantage to Salmonella in macrophages. Gut Microbes. 2019;10(3):412–423
   Google Scholar
• Prus E, Fibach E. Flow cytometry measurement of the labile iron pool in human hematopoietic cells. Cytometry A. 2008;73:22–27. doi:10.1002/cyto.a.20491.
   PubMed Web of Science ®Google Scholar