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Antimicrobial Agents That Inhibit the Outer Membrane Assembly Machines of Gram-Negative Bacteria

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초록

Gram-negative pathogens, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, pose a serious threat to public health worldwide, due to high rates of antibiotic resistance and the lack of development of novel antimicrobial agents targeting Gram-negative bacteria. The outer membrane (OM) of Gram-negative bacteria is a unique architecture that acts as a potent permeability barrier against toxic molecules, such as antibiotics. The OM is composed of phospholipids, lipopolysaccharide (LPS), outer membrane β-barrel proteins (OMP), and lipoproteins. These components are synthesized in the cytoplasm or in the inner membrane, and are then selectively transported to the OM by the specific transport machines, including the Lol, BAM, and Lpt pathways. In this review, we summarize recent studies on the assembly systems of OM components and analyze studies for the development of inhibitors that target these systems. These analyses show that OM assembly machines have the potential to be a novel attractive drug target of Gram-negative bacteria.

Abstract

Gram-negative pathogens, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, pose a serious threat to public health worldwide, due to high rates of antibiotic resistance and the lack of development of novel antimicrobial agents targeting Gram-negative bacteria. The outer membrane (OM) of Gram-negative bacteria is a unique architecture that acts as a potent permeability barrier against toxic molecules, such as antibiotics. The OM is composed of phospholipids, lipopolysaccharide (LPS), outer membrane β-barrel proteins (OMP), and lipoproteins. These components are synthesized in the cytoplasm or in the inner membrane, and are then selectively transported to the OM by the specific transport machines, including the Lol, BAM, and Lpt pathways. In this review, we summarize recent studies on the assembly systems of OM components and analyze studies for the development of inhibitors that target these systems. These analyses show that OM assembly machines have the potential to be a novel attractive drug target of Gram-negative bacteria.

참고문헌 (73)

  1. Patel DS, "Modeling and simulation of bacterial outer membranes and interactions with membrane proteins", Curr. Opin. Struct. Biol, 43, pp.131~140 (2017)
  2. May KL, "Making a membrane on the other side of the wall", Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1862, pp.1386~1393 (2017)
  3. Grabowicz M, "Lipoprotein transport : greasing the machines of outer membrane biogenesis : re-examining lipoprotein transport mechanisms among diverse Gramnegative bacteria while exploring new discoveries and questions", BioEssays, 40, pp.e1700187~ (2018)
  4. Typas A, "Regulation of peptidoglycan synthesis by outer-membrane proteins", Cell, 143, pp.1097~1109 (2010)
  5. Paradis-Bleau C, "Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases", Cell, 143, pp.1110~1120 (2010)
  6. Liu R, "Stepwise formation of the bacterial flagellar system", Proc. Natl. Acad. Sci. USA, 104, pp.7116~7121 (2007)
  7. Hospenthal MK, "A comprehensive guide to pilus biogenesis in Gram-negative bacteria", Nat. Rev. Microbiol, 15, pp.365~379 (2017)
  8. Durand E, "Biogenesis and structure of a type VI secretion membrane core complex", Nature, 523, pp.555~560 (2015)
  9. Dong C, "Wza the translocon for E. coli capsular polysaccharides defines a new class of membrane protein", Nature, 444, pp.226~229 (2006)
  10. Zeth K, "Porins in prokaryotes and eukaryotes:common themes and variations", Biochem. J, 431, pp.13~22 (2010)
  11. Lee CR, "Biology of Acinetobacter baumannii : pathogenesis, antibiotic resistance mechanisms, and prospective treatment options", Front. Cell. Infect. Microbiol, 7, pp.55~ (2017)
  12. O'Shea R, "Physicochemical properties of antibacterial compounds : implications for drug discovery", J. Med. Chem, 51, pp.2871~2878 (2008)
  13. Lee CR, "Strategies to minimize antibiotic resistance", Int. J. Environ. Res. Public Health, 10, pp.4274~4305 (2013)
  14. Lee CR, "Antimicrobial resistance of hypervirulent Klebsiella pneumoniae : epidemiology, hypervirulence-associated determinants, and resistance mechanisms", Front. Cell. Infect. Microbiol, 7, pp.483~ (2017)
  15. Konovalova A, "Outer membrane lipoprotein biogenesis: Lol is not the end", Philos. Trans. R. Soc. Lond. B. Biol. Sci, 370, pp.1679~ (2015)
  16. Narita SI, "Bacterial lipoproteins; biogenesis, sorting and quality control", Biochim. Biophys. Acta, 1862, pp.1414~1423 (2017)
  17. Yamaguchi K, "A single amino acid determinant of the membrane localization of lipoproteins in E. coli", Cell, 53, pp.423~432 (1988)
  18. Yakushi T, "A n ew ABC t r ansporter mediating the d etachment of lipid-modified proteins from membranes", Nat. Cell. Biol, 2, pp.212~218 (2000)
  19. Yakushi T, "LolAdependent release of a lipid-modified protein from the inner membrane of Escherichia coli requires nucleoside triphosphate", J. Biol. Chem, 273, pp.32576~32581 (1998)
  20. Mizutani M, "Functional differentiation of structurally similar membrane subunits of the ABC transporter LolCDE complex", FEBS Lett, 587, pp.23~29 (2013)
  21. Okuda S, "Model of mouth-to-mouth transfer of bacterial lipoproteins through inner membrane LolC, periplasmic LolA, and outer membrane LolB", Proc. Natl. Acad. Sci. USA, 106, pp.5877~5882 (2009)
  22. Takeda K, "Crystal structures of bacterial lipoprotein localization factors, LolA and LolB", EMBO J, 22, pp.3199~3209 (2003)
  23. Hayashi Y, "Roles of the protruding loop of factor B essential for the localization of lipoproteins(LolB)in the anchoring of bacterial triacylated proteins to the outer membrane", J. Biol. Chem, 289, pp.10530~10539 (2014)
  24. Walther DM, "Biogenesis of β-barrel membrane proteins in bacteria and eukaryotes : evolutionary conservation and divergence", Cell. Mol. Life Sci, 66, pp.2789~2804 (2009)
  25. Noinaj N, "The β-barrel membrane protein insertase machinery from Gram-negative bacteria", Curr. Opin. Struct. Biol, 31, pp.35~42 (2015)
  26. Voulhoux R, "Role of a highly conserved bacterial protein in outer membrane protein assembly", Science, 299, pp.262~265 (2003)
  27. Kim S, "Structure and function of an essential component of the outer membrane protein assembly machine", Science, 317, pp.961~964 (2007)
  28. Misra R, "In vivo roles of BamA, BamB and BamD in the biogenesis of BamA, a core protein of the β-barrel assembly machine of Escherichia coli", J. Mol. Biol, 427, pp.1061~1074 (2015)
  29. Hagan CL, "Bam lipoproteins assemble BamA in vitro", Biochemistry, 52, pp.6108~6113 (2013)
  30. Sperandeo P, "The lipopolysaccharide transport (Lpt) machinery: a nonconventional transporter for lipopolysaccharide assembly at the outer membrane of Gram-negative bacteria", J. Biol. Chem, 292, pp.17981~17990 (2017)
  31. Suits MD, "Novel structure of the conserved gram-negative lipopolysaccharide transport protein A and mutagenesis analysis", J. Mol. Biol, 380, pp.476~488 (2008)
  32. Merten JA, "Concentrationdependent oligomerization and oligomeric arrangement of LptA", Protein Sci, 21, pp.211~218 (2012)
  33. Freinkman E, "Regulated assembly of the transenvelope protein complex required for lipopolysaccharide export", Biochemistry, 51, pp.4800~4806 (2012)
  34. Okuda S, "Cytoplasmic ATP hydrolysis powers transport of lipopolysaccharide across the periplasm in E. coli", Science, 338, pp.1214~1217 (2012)
  35. Tran AX, "Structure and functional analysis of LptC, a conserved membrane protein involved in the lipopolysaccharide export pathway in Escherichia coli", J. Biol. Chem, 285, pp.33529~33539 (2010)
  36. Laguri C, "Interaction of lipopolysaccharides at i nter molecular sites of the periplasmic Lpt transport assembly", Sci. Rep, 7, pp.9715~ (2017)
  37. Schultz KM, "Lipopolysaccharide binding to the periplasmic protein LptA", Protein Sci, 26, pp.1517~1523 (2017)
  38. Freinkman E, "The complex that inserts lipopolysaccharide into the bacterial outer membrane forms a two-protein plug-and-barrel", Proc. Natl. Acad. Sci. USA, 108, pp.2486~2491 (2011)
  39. Gu Y, "Lipopolysaccharide is inserted into the outer membrane through an intramembrane hole, a lumen gate, and the lateral opening of LptD", Structure, 23, pp.496~504 (2015)
  40. Li X, "Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane", Sci. Rep, 5, pp.11883~ (2015)
  41. Sperandeo P, "Lipopolysaccharide biogenesis and transport at the outer membrane of Gram-negative bacteria", Biochim. Biophys. Acta, 1862, pp.1451~1460 (2017)
  42. Chng SS, "Disulfide rearrangement triggered by translocon assembly controls lipopolysaccharide export", Science, 337, pp.1665~1668 (2012)
  43. Chng SS, "Characterization of the two-protein complex in Escherichia coli responsible for lipopolysaccharide assembly at the outer membrane", Proc. Natl. Acad. Sci. USA, 107, pp.5363~5368 (2010)
  44. Chimalakonda G, "Lipoprotein LptE is required for the assembly of LptD by the beta-barrel assembly machine in the outer membrane of Escherichia coli", Proc. Natl. Acad. Sci. USA, 108, pp.2492~2497 (2011)
  45. Malojcic G, "LptE binds to and alters the physical state of LPS to catalyze its assembly at the cell surface", Proc. Natl. Acad. Sci. USA, 111, pp.9467~9472 (2014)
  46. Malinverni JC, "An ABC transport system that m aintains lipid a symmetry in the gram-negative outer membrane", Proc. Natl. Acad. Sci. USA, 106, pp.8009~8014 (2009)
  47. Ekiert DC, "Architectures of lipid transport systems for the bacterial outer membrane", Cell, 169, pp.273e217~285e217 (2017)
  48. Ruiz N, "Probing the barrier function of the outer membrane with chemical conditionality", ACS Chem. Biol, 1, pp.385~395 (2006)
  49. Dekker N, "Outer-membrane phospholipase A : known structure, unknown biological function", Mol. Microbiol, 35, pp.711~717 (2000)
  50. Bishop RE, "Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria", EMBO J, 19, pp.5071~5080 (2000)
  51. Chong ZS, "Osmoporin OmpC forms a complex with MlaA to maintain outer membrane lipid asymmetry in Escherichia coli", Mol. Microbiol, 98, pp.1133~1146 (2015)
  52. Dalebroux ZD, "Delivery of cardiolipins to the Salmonella outer membrane is necessary for survival within host tissues and virulence", Cell. Host Microbe, 17, pp.441~451 (2015)
  53. Ito H, "A new screening method to identify inhibitors of the Lol(localization of lipoproteins)system, a novel antibacterial target", Microbiol. Immunol, 51, pp.263~270 (2007)
  54. Pathania R, "Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting", Nat. Chem. Biol, 5, pp.849~856 (2009)
  55. Barker CA, "Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA", Bioorg. Med. Chem. Lett, 23, pp.2426~2431 (2013)
  56. Iwai N, "Novel S-benzylisothiourea compound that induces spherical cells in Escherichia coli probably by acting on a rod-shape-determining protein(s)other than penicillin-binding protein 2", Biosci. Biotechnol. Biochem, 66, pp.2658~2662 (2002)
  57. McLeod SM, "Small-molecule inhibitors of gram-negative lipoprotein trafficking discovered by phenotypic screening", J. Bacteriol, 197, pp.1075~1082 (2015)
  58. Nayar AS, "Novel antibacterial targets and compounds revealed by a high-throughput cell wall reporter assay", J. Bacteriol, 197, pp.1726~1734 (2015)
  59. Nickerson NN, "A novel inhibitor of the LolCDE ABC transporter essential for lipoprotein trafficking in Gram-negative bacteria", Antimicrob. Agents Chemother, 62, pp.4~ (2018)
  60. Sun D, "A pathway-specific cell based screening system to detect bacterial cell wall inhibitors", J. Antibiot. (Tokyo), 55, pp.279~287 (2002)
  61. Tam C, "Changes in lipopolysaccharide structure induce the σE-dependent response of Escherichia coli", Mol. Microbiol, 55, pp.1403~1412 (2005)
  62. Lima S, "Dual molecular signals mediate the bacterial response to outermembrane stress", Science, 340, pp.837~841 (2013)
  63. Gronenberg LS, "Development of an activity assay for discovery of inhibitors of lipopolysaccharide transport", J. Am. Chem. Soc, 132, pp.2518~2519 (2010)
  64. Sherman DJ, "Validation of inhibitors of an ABC transporter required to transport lipopolysaccharide to the cell surface in Escherichia coli", Bioorg. Med. Chem, 21, pp.4846~4851 (2013)
  65. Parker LL, "Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase", Science, 257, pp.1955~1957 (1992)
  66. Kokryakov VN, "Protegrins : leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins", FEBS Lett, 327, pp.231~236 (1993)
  67. Steinberg DA, "Protegrin-1 : a broad-spectrum, rapidly microbicidal peptide with in vivo activity", Antimicrob. Agents Chemother, 41, pp.1738~1742 (1997)
  68. Srinivas N, "Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa", Science, 327, pp.1010~1013 (2010)
  69. Andolina G, "A peptidomimetic antibiotic interacts with the periplasmic domain of LptD from Pseudomonas aeruginosa", ACS Chem. Biol, 13, pp.666~675 (2018)
  70. Schmidt J, "Structural studies of β-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp", Bioorg. Med. Chem, 21, pp.5806~5810 (2013)
  71. Vetterli SU, "Synthesis and antimicrobial activity against Pseudomonas aeruginosa of macrocyclic β-hairpin peptidomimetic antibiotics containing N-methylated amino acids", Bioorg. Med. Chem, 24, pp.6332~6339 (2016)
  72. Zerbe K, "Protein epitope mimetics : from new antibiotics to supramolecular synthetic vaccines", Acc. Chem. Res, 50, pp.1323~1331 (2017)
  73. Urfer M, "A peptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in Escherichia coli", J. Biol. Chem, 291, pp.1921~1932 (2016)

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