Abstract
Salmochelins represent novel carbohydrate containing catecholate siderophores, which are excreted by Salmonella enterica and uropathogenic Escherichia coli strains under low-iron stress. While previous analytical data showed salmochelins to contain 2,3-dihydroxybenzoyl-L-serine and glucose, the molecular structure remained elusive. Structure elucidation with electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), GC-MS and 2D-NMR now revealed that salmochelins are enterobactin-related compounds, which are β-C-glucosylated at the 5-position of a 2,3-dihydroxybenzoyl residue. The key compound salmochelin S4 is a twofold β-C-glucosylated enterobactin analogue. Comparison of partial structures of salmochelin with a C-glycosylated compound previously characterized by another group strongly suggest that salmochelins represent the long sought compounds termed Salmonella resistance factors (SRF) or pacifarins. Transformation of iro-genes into enterobactin-producing E. coli K12 confers the ability to produce salmochelins. A detailed analysis proved iroB to be the sole gene with glycosyltransferase activity necessary for salmochelin production. Salmochelins compared to enterobactin are the better siderophores in the presence of serum albumin. This may indicate for salmochelins a considerably more important role for pathogenic processes in certain Escherichia coli and Salmonella infections than formerly assigned to enterobactin. This conclusion is supported by the location of the iro genes on pathogenicity islands of uropathogenic E. coli strains.
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References
Bäumler AJ, Tsolis RM, van der Velden AW, Stojiljkovic I, Anic S, Heffron F. 1996 Identification of a new iron regulated locus of Salmonella typhi. Gene 183, 207-213
Bjarnason J, Southward CM, Surette MG. 2003 Genomic profiling of iron-responsive genes in Salmonella enterica serovar typhimurium by high-throughput screening of a random promoter library. J Bacteriol 185, 4973-4982
Braun V. 2001 Iron uptake mechanisms and their regulation in pathogenic bacteria. Int J Med Microbiol 291, 67-79
Braun V, Hantke K. 2001 Mechanisms of bacterial iron transport. In Microbial Transport Systems, ed. G Winkelmann, pp. 289-311. Weinheim: Wiley-VCH
Dobrindt U, Blum-Oehler G, Hartsch T, Gottschalk G, Ron EZ, Fünfstück R, Hacker J. 2001 S-Fimbria-encoding determinant sfa(I) is located on pathogenicity island III(536) of uropathogenic Escherichia coli strain 536. Infect Immun 69, 4248-4256
Dozois CM, Daigle F, Curtiss R, III. 2003 Identification of pathogen-specific and conserved genes expressed in vivo by an avian pathogenic Escherichia coli strain. Proc Natl Acad Sci USA 100, 247-252
Dromowicz M, Koell P. 1998 Syntheses of 2,6-anhydroaldonic acids from the corresponding anhydrodeoxynitroalditiols (glycopyranosylnitromethanes) and their conversion into methyl esters, amides and alditols. Carbohydrate Res 311, 103-119
Eriksson S, Lucchini S, Thompson A, Rhen M, Hinton JC. 2003 Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica. Mol Microbiol 47, 103-118
Foster JW. 2000 Microbial response to acid stress. In Bacterial stress response, ed. G Stroz, R Hengge-Aronis, pp. 99-115. ASM Press, Washington D. C.
Frank H, Nicholson G, Bayer E. 1978 Enantiomer labelling, a method for the quantitavie analysis of amino acids. J Chromatogr 167, 187-196
Fu JM. 1985 The structure elucidation of methyl pacifarinic acid. PhD thesis, University of Illinois, Chicago
Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. 2002 The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10, 1033-1043
Gorbacheva VY, Faundez G, Godfrey HP, Cabello FC. 2001 Restricted growth of ent(-) and tonB mutants of Salmonella enterica serovar Typhi in human Mono Mac 6 monocytic cells. FEMS Microbiol Lett 196, 7-11
Hantke K, Nicholson G, Rabsch W, Winkelmann G. 2003 Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN. Proc Natl Acad Sci USA 100, 3677-3682
Hoffmeister D, Drager G, Ichinose K, Rohr J, Bechthold A. 2003 The C-Glycosyltransferase UrdGT2 is unselective toward D-and L-configured nucleotide-bound rhodinoses. J Am Chem Soc 125, 4678-4679
Konopka K, Neilands JB. 1984 Effect of serum albumin on siderophore-mediated utilization of transferrin iron. Biochemistry 23, 2122-2127
Narayanan V, Seshadri TR. 1971 Paniculatin, a New Isoflavone-di-C-glucoside of Dalbergia paniculata Bark. Ind J Chem 9, 14-16
O'Brien IG, Gibson F. 1970 The structure of enterochelin and related 2,3-dihydroxy-N-benzoylserine conjugates from Escherichia coli. Biochim Biophys Acta 215, 393-402
Pollack JR, Neilands JB. 1970 Enterobactin, an iron transport compound from Salmonella typhimurium. Biochem Biophys Res Commun 38, 989-992
Porra RJ, Langman L, Young IG, Gibson F. 1972 The role of ferric enterochelin esterase in enterochelin-mediated iron transport and ferrochelatase activity in Escherichia coli. Arch Biochem Biophys 153, 74-78
Rabsch W, Methner U, Voigt W, Tschape H, Reissbrodt R, Williams PH. 2003 Role of receptor proteins for enterobactin and 2,3-dihydroxybenzoylserine in virulence of Salmonella enterica. Infect Immun 71, 6953-6961
Raymond KN, Dertz EA, Kim SS. 2003 Enterobactin: an archetype for microbial iron transport. Proc Natl Acad Sci USA 100, 3584-3588
Roche ED, Walsh CT. 2003 Dissection of the EntF condensation domain boundary and active site residues in nonribosomal peptide synthesis. Biochemistry 42, 1334-1344
Schneider HA. 1967 Ecological ectocrines in experimental epidemiology. A new class, the 'pacifarins', is delineated in the nutritional ecology of mouse salmonellosis. Science 158, 597-603
Sorsa LJ, Dufke S, Heesemann J, Schubert S. 2003 Characterization of an iroBCDEN gene cluster on a transmissible plasmid of uro-pathogenic Escherichia coli: evidence for horizontal transfer of a chromosomal virulence factor. Infect Immun 71, 3285-3293
Tsolis RM, Baumler AJ, Heffron F, Stojiljkovic I. 1996 Contribution of TonB-and Feo-mediated iron uptake to growth of Salmonella typhimurium in the mouse. Infect Immun 64, 4549-4556
Wang RF, Kushner SR. 1991 Construction of versatile low-copynumber vectors for cloning, sequencing and gene expression in Escherichia coli. Gene 100, 195-199
Wawszkiewicz EJ, Schneider HA, Starcher B, Pollack J, Neilands JB. 1971 Salmonellosis pacifarin activity of enterobactin. Proc Natl Acad Sci USA 68, 2870-2873
Wawszkiewicz EJ. 1975 Riddle of pacifarins in Microbiology-1974. (Ed. Schlesinger, MJ) pp. 299-305. ASM, Washington D.C., USA
Weinberg ED. 1978 Iron and infection. Microbiol Rev 42, 45-66
Winkelmann G, Cansier A, Beck W, Jung G. 1994 HPLC separation of enterobactin and linear 2,3-dihydroxybenzoylserine derivatives: a study on mutants of Escherichia coli defective in regulation (fur), esterase (fes) and transport (fepA). Biometals 7, 149-154
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Bister, B., Bischoff, D., Nicholson, G.J. et al. The structure of salmochelins: C-glucosylated enterobactins of Salmonella enterica § . Biometals 17, 471–481 (2004). https://doi.org/10.1023/B:BIOM.0000029432.69418.6a
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DOI: https://doi.org/10.1023/B:BIOM.0000029432.69418.6a