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Pathway Description
Polymyxin Resistance
Escherichia coli
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2015-10-08
Last Updated: 2019-08-13
UDP-glucuronic acid compound undergoes a NAD dependent reaction through a bifunctional polymyxin resistance protein to produce UDP-Beta-L-threo-pentapyranos-4-ulose. This compound then reacts with L-glutamic acid through a UDP-4-amino-4-deoxy-L-arabinose--oxoglutarate aminotransferase to produce an oxoglutaric acid and UDP-4-amino-4-deoxy-beta-L-arabinopyranose The latter compound interacts with a N10-formyl-tetrahydrofolate through a bifunctional polymyxin resistance protein ArnA, resulting in a tetrahydrofolate, a hydrogen ion and a UDP-4-deoxy-4-formamido-beta-L-arabinopyranose, which in turn reacts with a product of the methylerythritol phosphate and polysoprenoid biosynthesis pathway, di-trans,octa-cis-undecaprenyl phosphate to produce a 4-deoxy-4-formamido-alpha-L-arabinopyranosyl ditrans, octacis-undecaprenyl phosphate.
The compound 4-deoxy-4-formamido-alpha-L-arabinopyranosyl ditrans, octacis-undecaprenyl phosphate hypothetically reacts with water and results in the release of a formic acid and 4-amino-4-deoxy-α-L-arabinopyranosyl ditrans,octacis-undecaprenyl phosphate which in turn reacts with a KDO2-lipid A through a 4-amino-4-deoxy-L-arabinose transferase resulting in the release of a di-trans,octa-cis-undecaprenyl phosphate and a L-Ara4N-modified KDO2-Lipid A
References
Polymyxin Resistance References
Barchiesi J, Espariz M, Checa SK, Soncini FC: Downregulation of RpoN-controlled genes protects Salmonella cells from killing by the cationic antimicrobial peptide polymyxin B. FEMS Microbiol Lett. 2009 Feb;291(1):73-9. doi: 10.1111/j.1574-6968.2008.01437.x. Epub 2008 Dec 3.
Pubmed: 19076233
Bretscher LE, Morrell MT, Funk AL, Klug CS: Purification and characterization of the L-Ara4N transferase protein ArnT from Salmonella typhimurium. Protein Expr Purif. 2006 Mar;46(1):33-9. doi: 10.1016/j.pep.2005.08.028. Epub 2005 Sep 28.
Pubmed: 16226890
Fu W, Yang F, Kang X, Zhang X, Li Y, Xia B, Jin C: First structure of the polymyxin resistance proteins. Biochem Biophys Res Commun. 2007 Oct 5;361(4):1033-7. doi: 10.1016/j.bbrc.2007.07.144. Epub 2007 Aug 2.
Pubmed: 17686460
Gatzeva-Topalova PZ, May AP, Sousa MC: Structure and mechanism of ArnA: conformational change implies ordered dehydrogenase mechanism in key enzyme for polymyxin resistance. Structure. 2005 Jun;13(6):929-42. doi: 10.1016/j.str.2005.03.018.
Pubmed: 15939024
Groisman EA, Kayser J, Soncini FC: Regulation of polymyxin resistance and adaptation to low-Mg2+ environments. J Bacteriol. 1997 Nov;179(22):7040-5.
Pubmed: 9371451
Gunn JS: The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol. 2008 Jun;16(6):284-90. doi: 10.1016/j.tim.2008.03.007. Epub 2008 May 6.
Pubmed: 18467098
Kline T, Trent MS, Stead CM, Lee MS, Sousa MC, Felise HB, Nguyen HV, Miller SI: Synthesis of and evaluation of lipid A modification by 4-substituted 4-deoxy arabinose analogs as potential inhibitors of bacterial polymyxin resistance. Bioorg Med Chem Lett. 2008 Feb 15;18(4):1507-10. doi: 10.1016/j.bmcl.2007.12.061. Epub 2007 Dec 27.
Pubmed: 18187325
Kox LF, Wosten MM, Groisman EA: A small protein that mediates the activation of a two-component system by another two-component system. EMBO J. 2000 Apr 17;19(8):1861-72. doi: 10.1093/emboj/19.8.1861.
Pubmed: 10775270
Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A 3rd, Forrest A, Bulitta JB, Tsuji BT: Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy. 2010 Dec;30(12):1279-91. doi: 10.1592/phco.30.12.1279.
Pubmed: 21114395
Nummila K, Kilpelainen I, Zahringer U, Vaara M, Helander IM: Lipopolysaccharides of polymyxin B-resistant mutants of Escherichia coli are extensively substituted by 2-aminoethyl pyrophosphate and contain aminoarabinose in lipid A. Mol Microbiol. 1995 Apr;16(2):271-8.
Pubmed: 7565089
Pilonieta MC, Erickson KD, Ernst RK, Detweiler CS: A protein important for antimicrobial peptide resistance, YdeI/OmdA, is in the periplasm and interacts with OmpD/NmpC. J Bacteriol. 2009 Dec;191(23):7243-52. doi: 10.1128/JB.00688-09. Epub 2009 Sep 18.
Pubmed: 19767429
Raetz CR, Whitfield C: Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002;71:635-700. doi: 10.1146/annurev.biochem.71.110601.135414. Epub 2001 Nov 9.
Pubmed: 12045108
Trent MS, Ribeiro AA, Doerrler WT, Lin S, Cotter RJ, Raetz CR: Accumulation of a polyisoprene-linked amino sugar in polymyxin-resistant Salmonella typhimurium and Escherichia coli: structural characterization and transfer to lipid A in the periplasm. J Biol Chem. 2001 Nov 16;276(46):43132-44. doi: 10.1074/jbc.M106962200. Epub 2001 Sep 4.
Pubmed: 11535605
Wosten MM, Kox LF, Chamnongpol S, Soncini FC, Groisman EA: A signal transduction system that responds to extracellular iron. Cell. 2000 Sep 29;103(1):113-25.
Pubmed: 11051552
Yan A, Guan Z, Raetz CR: An undecaprenyl phosphate-aminoarabinose flippase required for polymyxin resistance in Escherichia coli. J Biol Chem. 2007 Dec 7;282(49):36077-89. doi: 10.1074/jbc.M706172200. Epub 2007 Oct 10.
Pubmed: 17928292
Zhou Z, Lin S, Cotter RJ, Raetz CR: Lipid A modifications characteristic of Salmonella typhimurium are induced by NH4VO3 in Escherichia coli K12. Detection of 4-amino-4-deoxy-L-arabinose, phosphoethanolamine and palmitate. J Biol Chem. 1999 Jun 25;274(26):18503-14.
Pubmed: 10373459
Breazeale SD, Ribeiro AA, Raetz CR: Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinose. J Biol Chem. 2002 Jan 25;277(4):2886-96. doi: 10.1074/jbc.M109377200. Epub 2001 Nov 8.
Pubmed: 11706007
Yamamoto Y, Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kimura S, Kitagawa M, Makino K, Miki T, Mitsuhashi N, Mizobuchi K, Mori H, Nakade S, Nakamura Y, Nashimoto H, Oshima T, Oyama S, Saito N, Sampei G, Satoh Y, Sivasundaram S, Tagami H, Horiuchi T, et al.: Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features. DNA Res. 1997 Apr 28;4(2):91-113. doi: 10.1093/dnares/4.2.91.
Pubmed: 9205837
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. doi: 10.1038/msb4100049. Epub 2006 Feb 21.
Pubmed: 16738553
Breazeale SD, Ribeiro AA, McClerren AL, Raetz CR: A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function oF UDP-4-deoxy-4-formamido-L-arabinose. J Biol Chem. 2005 Apr 8;280(14):14154-67. doi: 10.1074/jbc.M414265200. Epub 2005 Jan 28.
Pubmed: 15695810
Trent MS, Ribeiro AA, Lin S, Cotter RJ, Raetz CR: An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor. J Biol Chem. 2001 Nov 16;276(46):43122-31. doi: 10.1074/jbc.M106961200. Epub 2001 Sep 4.
Pubmed: 11535604
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