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Potential Target Sites that Are Affected by Antimicrobial Surfaces

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Part of the Materials Horizons: From Nature to Nanomaterials book series (MHFNN)

Abstract

Antimicrobial targets should be essential to the life or pathogenicity of bacteria and contain conserved target binding regions. This chapter reviews the antimicrobial target sites, their structures, roles, and their inhibition. Life-essential targets include FtsZ and their regulatory proteins; they mediate the cell division and its accompanying modifications in the cell wall. Peptidoglycan biosynthesis enzymes also belong to life-essential targets; we focused on the integral membrane protein MraY, the membrane-associated protein MurG, and penicillin-binding proteins (PBPs) rather than Mur enzymes due to their in vivo inaccessibility. Targeting DNA, as an essential element, may damage the strands or interfere with the replication mechanisms, or even specific genes; sequence-specific binders are designed. For expanding the drug targets, bacterial quorum sensing systems (QSs) are targeted; it regulates several genes; we reviewed the quorum quenching through several approaches. Other targets would provide new anti-virulence drugs. The d-alanylation of teichoic acid represents a potential target in Gram-positive bacteria; we discussed the specificity and inter-species conservation of the key enzyme (d-Alanyl carrier protein ligase) in this pathway.

Keywords

Autoinducing peptides Divisome DltA FtsZ MraY MurG N-acyl-homoserine lactones PBPs Quorum quenching 

References

  1. 1.
    Lange RP, Locher HH, Wyss PC, Then RL (2007) The targets of currently used antibacterial agents: lessons for drug discovery. Curr Pharm Des 13(30):3140–3154CrossRefGoogle Scholar
  2. 2.
    Okano A, Isley NA, Boger DL (2017) Peripheral modifications of [Ψ [CH2NH] Tpg4] vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics. Proc Natl Acad Sci 114(26):E5052–E5061Google Scholar
  3. 3.
    Bromham L (2009) Why do species vary in their rate of molecular evolution? Biol Let 5(3):401–404CrossRefGoogle Scholar
  4. 4.
    Dunning Hotopp JC (2011) Horizontal gene transfer between bacteria and animals. Trends Genet (Regular ed) 27(4):157–163CrossRefGoogle Scholar
  5. 5.
    Fernandes P (2006) Antibacterial discovery and development—the failure of success? Nat Biotechnol 24(12):1497CrossRefGoogle Scholar
  6. 6.
    Cain R, Narramore S, McPhillie M, Simmons K, Fishwick CW (2014) Applications of structure-based design to antibacterial drug discovery. Bioorg Chem 55:69–76CrossRefGoogle Scholar
  7. 7.
    Rothfield LI, Justice SS (1997) Bacterial cell division: the cycle of the ring. Cell 88(5):581–584CrossRefGoogle Scholar
  8. 8.
    Egan AJ, Vollmer W (2013) The physiology of bacterial cell division. Ann NY Acad Sci 1277(1):8–28CrossRefGoogle Scholar
  9. 9.
    Harry E, Monahan L, Thompson L (2006) Bacterial cell division: the mechanism and its precison. Int Rev Cytol 253:27–94CrossRefGoogle Scholar
  10. 10.
    Aarsman ME, Piette A, Fraipont C, Vinkenvleugel TM, Nguyen-Distèche M, den Blaauwen T (2005) Maturation of the Escherichia coli divisome occurs in two steps. Mol Microbiol 55(6):1631–1645CrossRefGoogle Scholar
  11. 11.
    van der Ploeg R, Verheul J, Vischer NO, Alexeeva S, Hoogendoorn E, Postma M, Banzhaf M, Vollmer W, den Blaauwen T (2013) Colocalization and interaction between elongasome and divisome during a preparative cell division phase in Escherichia coli. Mol Microbiol 87(5):1074–1087CrossRefGoogle Scholar
  12. 12.
    Blaauwen Td, Andreu JM, Monasterio O (2014) Bacterial cell division proteins as antibiotic targets. Bioorg Chem 55:27–38CrossRefGoogle Scholar
  13. 13.
    Vaughan S, Wickstead B, Gull K, Addinall SG (2004) Molecular evolution of FtsZ protein sequences encoded within the genomes of archaea, bacteria, and eukaryota. J Mol Evol 58(1):19–29CrossRefGoogle Scholar
  14. 14.
    Romberg L, Levin PA (2003) Assembly dynamics of the bacterial cell division protein FtsZ: poised at the edge of stability. Annu Rev Microbiol 57(1):125–154CrossRefGoogle Scholar
  15. 15.
    Goehring NW, Gueiros-Filho F, Beckwith J (2005) Premature targeting of a cell division protein to midcell allows dissection of divisome assembly in Escherichia coli. Genes Dev 19(1):127–137CrossRefGoogle Scholar
  16. 16.
    Margolin W (2005) FtsZ and the division of prokaryotic cells and organelles. Nat Rev Mol Cell Biol 6(11):862CrossRefGoogle Scholar
  17. 17.
    Weiss DS (2004) Bacterial cell division and the septal ring. Mol Microbiol 54(3):588–597CrossRefGoogle Scholar
  18. 18.
    Anderson DE, Gueiros-Filho FJ, Erickson HP (2004) Assembly dynamics of FtsZ rings in Bacillus subtilis and Escherichia coli and effects of FtsZ-regulating proteins. J Bacteriol 186(17):5775–5781CrossRefGoogle Scholar
  19. 19.
    Meier EL, Goley ED (2014) Form and function of the bacterial cytokinetic ring. Curr Opin Cell Biol 26:19–27CrossRefGoogle Scholar
  20. 20.
    Chen Y, Milam SL, Erickson HP (2012) SulA inhibits assembly of FtsZ by a simple sequestration mechanism. Biochemistry 51(14):3100–3109CrossRefGoogle Scholar
  21. 21.
    Handler AA, Lim JE, Losick R (2008) Peptide inhibitor of cytokinesis during sporulation in Bacillus subtilis. Mol Microbiol 68(3):588–599CrossRefGoogle Scholar
  22. 22.
    Läppchen T, Pinas VA, Hartog AF, Koomen G-J, Schaffner-Barbero C, Andreu JM, Trambaiolo D, Löwe J, Juhem A, Popov AV (2008) Probing FtsZ and tubulin with C8-substituted GTP analogs reveals differences in their nucleotide binding sites. Chem Biol 15(2):189–199CrossRefGoogle Scholar
  23. 23.
    Matsui T, Yamane J, Mogi N, Yamaguchi H, Takemoto H, Yao M, Tanaka I (2012) Structural reorganization of the bacterial cell-division protein FtsZ from Staphylococcus aureus. Acta Crystallogr D Biol Crystallogr 68(9):1175–1188CrossRefGoogle Scholar
  24. 24.
    Leung AK, White EL, Ross LJ, Reynolds RC, DeVito JA, Borhani DW (2004) Structure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches. J Mol Biol 342(3):953–970CrossRefGoogle Scholar
  25. 25.
    Oliva MA, Trambaiolo D, Löwe J (2007) Structural insights into the conformational variability of FtsZ. J Mol Biol 373(5):1229–1242CrossRefGoogle Scholar
  26. 26.
    Mendieta J, Rico AI, López-Viñas E, Vicente M, Mingorance J, Gómez-Puertas P (2009) Structural and functional model for ionic (K+/Na+) and pH dependence of GTPase activity and polymerization of FtsZ, the prokaryotic ortholog of tubulin. J Mol Biol 390(1):17–25CrossRefGoogle Scholar
  27. 27.
    Scheffers D-J, de Wit JG, den Blaauwen T, Driessen AJ (2002) GTP hydrolysis of cell division protein FtsZ: evidence that the active site is formed by the association of monomers. Biochemistry 41(2):521–529CrossRefGoogle Scholar
  28. 28.
    Thanedar S, Margolin W (2004) FtsZ exhibits rapid movement and oscillation waves in helix-like patterns in Escherichia coli. Curr Biol 14(13):1167–1173CrossRefGoogle Scholar
  29. 29.
    Popp D, Iwasa M, Narita A, Erickson HP, Maéda Y (2009) FtsZ condensates: an in vitro electron microscopy study. Biopolym: Original Res Biomol 91(5):340–350Google Scholar
  30. 30.
    González JM, Vélez M, Jiménez M, Alfonso C, Schuck P, Mingorance J, Vicente M, Minton AP, Rivas G (2005) Cooperative behavior of Escherichia coli cell-division protein FtsZ assembly involves the preferential cyclization of long single-stranded fibrils. Proc Natl Acad Sci 102(6):1895–1900CrossRefGoogle Scholar
  31. 31.
    Plaza A, Keffer JL, Bifulco G, Lloyd JR, Bewley CA (2010) Chrysophaentins A–H, antibacterial bisdiarylbutene macrocycles that inhibit the bacterial cell division protein FtsZ. J Am Chem Soc 132(26):9069–9077CrossRefGoogle Scholar
  32. 32.
    Marcelo F, Huecas S, Ruiz-Ávila LB, Cañada FJ, Perona A, Poveda A, Martín-Santamaría S, Morreale A, Jiménez-Barbero JS, Andreu JM (2013) Interactions of bacterial cell division protein FtsZ with C8-substituted guanine nucleotide inhibitors. A combined NMR, biochemical and molecular modeling perspective. J Am Chem Soc 135(44):16418–16428Google Scholar
  33. 33.
    Schaffner-Barbero C, Gil-Redondo R, Ruiz-Avila LB, Huecas S, Läppchen T, den Blaauwen T, Diaz JF, Morreale A, Andreu JM (2010) Insights into nucleotide recognition by cell division protein FtsZ from a mant-GTP competition assay and molecular dynamics. Biochemistry 49(49):10458–10472CrossRefGoogle Scholar
  34. 34.
    Buske P, Levin PA (2013) A flexible C-terminal linker is required for proper FtsZ assembly in vitro and cytokinetic ring formation in vivo. Mol Microbiol 89(2):249–263CrossRefGoogle Scholar
  35. 35.
    Gardner KAA, Moore DA, Erickson HP (2013) The C-terminal linker of Escherichia coli FtsZ functions as an intrinsically disordered peptide. Mol Microbiol 89(2):264–275CrossRefGoogle Scholar
  36. 36.
    Sundararajan K, Miguel A, Desmarais SM, Meier EL, Huang KC, Goley ED (2015) The bacterial tubulin FtsZ requires its intrinsically disordered linker to direct robust cell wall construction. Nat Commun 6:7281CrossRefGoogle Scholar
  37. 37.
    Haney SA, Glasfeld E, Hale C, Keeney D, He Z, de Boer P (2001) Genetic Analysis of the Escherichia coli FtsZ·ZipA Interaction in the Yeast Two-hybrid System characterization of ftsz residues essential for the interactions with zipa AND WITH FtsA. J Biol Chem 276(15):11980–11987CrossRefGoogle Scholar
  38. 38.
    den Blaauwen T (2013) Prokaryotic cell division: flexible and diverse. Curr Opin Microbiol 16(6):738–744CrossRefGoogle Scholar
  39. 39.
    Vicente M, Rico AI (2006) The order of the ring: assembly of Escherichia coli cell division components. Mol Microbiol 61(1):5–8CrossRefGoogle Scholar
  40. 40.
    Loose M, Mitchison TJ (2014) The bacterial cell division proteins FtsA and FtsZ self-organize into dynamic cytoskeletal patterns. Nat Cell Biol 16(1):38CrossRefGoogle Scholar
  41. 41.
    Feucht A, Lucet I, Yudkin MD, Errington J (2001) Cytological and biochemical characterization of the FtsA cell division protein of Bacillus subtilis. Mol Microbiol 40(1):115–125CrossRefGoogle Scholar
  42. 42.
    Rueda S, Vicente M, Mingorance J (2003) Concentration and assembly of the division ring proteins FtsZ, FtsA, and ZipA during the Escherichia coli cell cycle. J Bacteriol 185(11):3344–3351CrossRefGoogle Scholar
  43. 43.
    Krupka M, Cabré EJ, Jiménez M, Rivas G, Rico AI, Vicente M (2014) Role of the FtsA C terminus as a switch for polymerization and membrane association. MBio 5(6):e02221–02214CrossRefGoogle Scholar
  44. 44.
    Paradis-Bleau C, Sanschagrin F, Levesque RC (2005) Peptide inhibitors of the essential cell division protein FtsA. Protein Eng Des Sel 18(2):85–91CrossRefGoogle Scholar
  45. 45.
    Lara B, Rico AI, Petruzzelli S, Santona A, Dumas J, Biton J, Vicente M, Mingorance J, Massidda O (2005) Cell division in cocci: localization and properties of the Streptococcus pneumoniae FtsA protein. Mol Microbiol 55(3):699–711CrossRefGoogle Scholar
  46. 46.
    Margolin W (2000) Themes and variations in prokaryotic cell division. FEMS Microbiol Rev 24(4):531–548CrossRefGoogle Scholar
  47. 47.
    Hale CA, Rhee AC, De Boer PA (2000) ZipA-induced bundling of FtsZ polymers mediated by an interaction between C-terminal domains. J Bacteriol 182(18):5153–5166CrossRefGoogle Scholar
  48. 48.
    Mosyak L, Zhang Y, Glasfeld E, Haney S, Stahl M, Seehra J, Somers WS (2000) The bacterial cell division protein ZipA and its interaction with an FtsZ fragment revealed by X-ray crystallography. EMBO J 19(13):3179–3191CrossRefGoogle Scholar
  49. 49.
    Kenny CH, Ding W, Kelleher K, Benard S, Dushin EG, Sutherland AG, Mosyak L, Kriz R, Ellestad G (2003) Development of a fluorescence polarization assay to screen for inhibitors of the FtsZ/ZipA interaction. Anal Biochem 323(2):224–233CrossRefGoogle Scholar
  50. 50.
    Jennings LD, Foreman KW, Rush TS III, Tsao DH, Mosyak L, Kincaid SL, Sukhdeo MN, Sutherland AG, Ding W, Kenny CH (2004) Combinatorial synthesis of substituted 3-(2-indolyl) piperidines and 2-phenyl indoles as inhibitors of ZipA–FtsZ interaction. Bioorg Med Chem 12(19):5115–5131CrossRefGoogle Scholar
  51. 51.
    Rush TS, Grant JA, Mosyak L, Nicholls A (2005) A shape-based 3-D scaffold hopping method and its application to a bacterial protein–protein interaction. J Med Chem 48(5):1489–1495CrossRefGoogle Scholar
  52. 52.
    Camberg JL, Hoskins JR, Wickner S (2009) ClpXP protease degrades the cytoskeletal protein, FtsZ, and modulates FtsZ polymer dynamics. Proc Natl Acad Sci 106(26):10614–10619CrossRefGoogle Scholar
  53. 53.
    Ye F, Li J, Yang C-G (2017) The development of small-molecule modulators for ClpP protease activity. Mol BioSyst 13(1):23–31CrossRefGoogle Scholar
  54. 54.
    Lee B-G, Park EY, Lee K-E, Jeon H, Sung KH, Paulsen H, Rübsamen-Schaeff H, Brötz-Oesterhelt H, Song HK (2010) Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism. Nat Struct Mol Biol 17(4):471CrossRefGoogle Scholar
  55. 55.
    Sass P, Josten M, Famulla K, Schiffer G, Sahl H-G, Hamoen L, Brötz-Oesterhelt H (2011) Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ. Proc Natl Acad Sci 108(42):17474–17479CrossRefGoogle Scholar
  56. 56.
    Schmidt KL, Peterson ND, Kustusch RJ, Wissel MC, Graham B, Phillips GJ, Weiss DS (2004) A predicted ABC transporter, FtsEX, is needed for cell division in Escherichia coli. J Bacteriol 186(3):785–793CrossRefGoogle Scholar
  57. 57.
    Pichoff S, Du S, Lutkenhaus J (2019) Roles of FtsEX in cell division. Res Microbiol (in press)Google Scholar
  58. 58.
    Sham LT, Barendt SM, Kopecky KE, Winkler ME (2011) Essential PcsB putative peptidoglycan hydrolase interacts with the essential FtsXSpn cell division protein in Streptococcus pneumoniae D39. Proc Natl Acad Sci 108(45):E1061–E1069CrossRefGoogle Scholar
  59. 59.
    Mohamed M, Awad S, Ahmed N (2011) Synthesis and antimicrobial evaluation of some 6-aryl-5-cyano-2-thiouracil derivatives. Acta Pharm 61(2):171–185CrossRefGoogle Scholar
  60. 60.
    Taguchi A, Welsh MA, Marmont LS, Lee W, Sjodt M, Kruse AC, Kahne D, Bernhardt TG, Walker S (2019) FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein. Nat Microbiol 4(4):587CrossRefGoogle Scholar
  61. 61.
    Mohammadi T, Sijbrandi R, Lutters M, Verheul J, Martin NI, den Blaauwen T, de Kruijff B, Breukink E (2014) Specificity of the transport of lipid II by FtsW in Escherichia coli. J Biol Chem 289(21):14707–14718CrossRefGoogle Scholar
  62. 62.
    Gonzalez MD, Akbay EA, Boyd D, Beckwith J (2010) Multiple interaction domains in FtsL, a protein component of the widely conserved bacterial FtsLBQ cell division complex. J Bacteriol 192(11):2757–2768CrossRefGoogle Scholar
  63. 63.
    Tsang MJ, Bernhardt TG (2015) A role for the FtsQLB complex in cytokinetic ring activation revealed by an ftsL allele that accelerates division. Mol Microbiol 95(6):925–944CrossRefGoogle Scholar
  64. 64.
    Choi Y, Kim J, Yoon HJ, Jin KS, Ryu S, Lee HH (2018) Structural insights into the FtsQ/FtsB/FtsL complex, a key component of the divisome. Sci Rep 8(1):18061CrossRefGoogle Scholar
  65. 65.
    Bramkamp M, Weston L, Daniel RA, Errington J (2006) Regulated intramembrane proteolysis of FtsL protein and the control of cell division in Bacillus subtilis. Mol Microbiol 62(2):580–591CrossRefGoogle Scholar
  66. 66.
    Löfmark S, Edlund C, Nord CE (2010) Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis 50(Supplement_1):S16–S23Google Scholar
  67. 67.
    Wagenlehner FM, Wullt B, Perletti G (2011) Antimicrobials in urogenital infections. Int J Antimicrob Agents 38:3–10CrossRefGoogle Scholar
  68. 68.
    Baraldi PG, Bovero A, Fruttarolo F, Preti D, Tabrizi MA, Pavani MG, Romagnoli R (2004) DNA minor groove binders as potential antitumor and antimicrobial agents. Med Res Rev 24(4):475–528CrossRefGoogle Scholar
  69. 69.
    Pindur U, Jansen M, Lemster T (2005) Advances in DNA-ligands with groove binding, intercalating and/or alkylating activity: chemistry, DNA-binding and biology. Curr Med Chem 12(24):2805–2847CrossRefGoogle Scholar
  70. 70.
    Richards AD, Rodger A (2007) Synthetic metallomolecules as agents for the control of DNA structure. Chem Soc Rev 36(3):471–483CrossRefGoogle Scholar
  71. 71.
    Waksman SA, Woodruff HB (1940) The soil as a source of microorganisms antagonistic to disease-producing bacteria. J Bacteriol 40(4):581CrossRefGoogle Scholar
  72. 72.
    Paramanathan T, Vladescu I, McCauley MJ, Rouzina I, Williams MC (2012) Force spectroscopy reveals the DNA structural dynamics that govern the slow binding of Actinomycin D. Nucleic Acids Res 40(11):4925–4932CrossRefGoogle Scholar
  73. 73.
    Zolova OE, Mady AS, Garneau-Tsodikova S (2010) Recent developments in bisintercalator natural products. Biopolymers 93(9):777–790CrossRefGoogle Scholar
  74. 74.
    Bolhuis A, Aldrich-Wright JR (2014) DNA as a target for antimicrobials. Bioorg Chem 55:51–59CrossRefGoogle Scholar
  75. 75.
    Haq I, Ladbury JE, Chowdhry BZ, Jenkins TC, Chaires JB (1997) Specific binding of Hoechst 33258 to the d (CGCAAATTTGCG) 2 duplex: calorimetric and spectroscopic studies. J Mol Biol 271(2):244–257CrossRefGoogle Scholar
  76. 76.
    Cory M, Tidwell RR, Fairley TA (1992) Structure and DNA binding activity of analogs of 1,5-bis(4-amidinophenoxy)pentane (pentamidine). J Med Chem 35(3):431–438CrossRefGoogle Scholar
  77. 77.
    Montazerozohori M, Zahedi S, Naghiha A, Zohour MM (2014) Synthesis, characterization and thermal behavior of antibacterial and antifungal active zinc complexes of bis (3(4-dimethylaminophenyl)-allylidene-1,2-diaminoethane. Mater Sci Eng, C 35:195–204CrossRefGoogle Scholar
  78. 78.
    Pelton JG, Wemmer DE (1989) Structural characterization of a 2: 1 distamycin Ad (CGCAAATTGGC) complex by two-dimensional NMR. Proc Natl Acad Sci 86(15):5723–5727CrossRefGoogle Scholar
  79. 79.
    Ginsburg H, Nissani E, Krugliak M, Williamson DH (1993) Selective toxicity to malaria parasites by non-intercalating DNA-binding ligands. Mol Biochem Parasitol 58(1):7–15CrossRefGoogle Scholar
  80. 80.
    Dervan PB, Bürli RW (1999) Sequence-specific DNA recognition by polyamides. Curr Opin Chem Biol 3(6):688–693CrossRefGoogle Scholar
  81. 81.
    Morinaga H, Bando T, Takagaki T, Yamamoto M, Hashiya K, Sugiyama H (2011) Cysteine cyclic pyrrole–imidazole polyamide for sequence-specific recognition in the DNA minor groove. J Am Chem Soc 133(46):18924–18930CrossRefGoogle Scholar
  82. 82.
    Howson SE, Bolhuis A, Brabec V, Clarkson GJ, Malina J, Rodger A, Scott P (2012) Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity. Nat Chem 4(1):31CrossRefGoogle Scholar
  83. 83.
    Bhaduri S, Ranjan N, Arya DP (2018) An overview of recent advances in duplex DNA recognition by small molecules. Beilstein J Org Chem 14(1):1051–1086CrossRefGoogle Scholar
  84. 84.
    Steffens LS, Nicholson S, Paul LV, Nord CE, Patrick S, Abratt VR (2010) Bacteroides fragilis RecA protein overexpression causes resistance to metronidazole. Res Microbiol 161(5):346–354CrossRefGoogle Scholar
  85. 85.
    Lomovskaya N, Hong S-K, Kim S-U, Fonstein L, Furuya K, Hutchinson R (1996) The Streptomyces peucetius drrC gene encodes a UvrA-like protein involved in daunorubicin resistance and production. J Bacteriol 178(11):3238–3245CrossRefGoogle Scholar
  86. 86.
    Watanabe K, Hotta K, Praseuth AP, Koketsu K, Migita A, Boddy CN, Wang CC, Oguri H, Oikawa H (2006) Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. Nat Chem Biol 2(8):423CrossRefGoogle Scholar
  87. 87.
    Moore JM, Salama NR (2005) Mutational analysis of metronidazole resistance in Helicobacter pylori. Antimicrob Agents Chemother 49(3):1236–1237CrossRefGoogle Scholar
  88. 88.
    Reysset G (1996) Genetics of 5-Nitroimidazole resistance in Bacteroides species. Anaerobe 2(2):59–69CrossRefGoogle Scholar
  89. 89.
    Sparr C, Purkayastha N, Kolesinska B, Gengenbacher M, Amulic B, Matuschewski K, Seebach D, Kamena F (2013) Improved efficacy of fosmidomycin against Plasmodium and Mycobacterium species by combination with the cell-penetrating peptide octaarginine. Antimicrob Agents Chemother 57(10):4689–4698CrossRefGoogle Scholar
  90. 90.
    Matteï PJ, Neves D, Dessen A (2010) Bridging cell wall biosynthesis and bacterial morphogenesis. Curr Opin Struct Biol 20(6):749–755CrossRefGoogle Scholar
  91. 91.
    Gautam A, Vyas R, Tewari R (2011) Peptidoglycan biosynthesis machinery: a rich source of drug targets. Crit Rev Biotechnol 31(4):295–336CrossRefGoogle Scholar
  92. 92.
    Barreteau H, Kovač A, Boniface A, Sova M, Gobec S, Blanot D (2008) Cytoplasmic steps of peptidoglycan biosynthesis. FEMS Microbiol Rev 32(2):168–207CrossRefGoogle Scholar
  93. 93.
    Bouhss A, Trunkfield AE, Bugg TD, Mengin-Lecreulx D (2007) The biosynthesis of peptidoglycan lipid-linked intermediates. FEMS Microbiol Rev 32(2):208–233CrossRefGoogle Scholar
  94. 94.
    Crouvoisier M, Mengin-Lecreulx D, van Heijenoort J (1999) UDP-N-acetylglucosamine: N-acetylmuramoyl-(pentapeptide) pyrophosphoryl undecaprenol N-acetylglucosamine transferase from Escherichia coli: overproduction, solubilization, and purification. FEBS Lett 449(2–3):289–292CrossRefGoogle Scholar
  95. 95.
    Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P (2008) The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev 32(2):234–258CrossRefGoogle Scholar
  96. 96.
    Bugg TD, Braddick D, Dowson CG, Roper DI (2011) Bacterial cell wall assembly: still an attractive antibacterial target. Trends Biotechnol 29(4):167–173CrossRefGoogle Scholar
  97. 97.
    Silver LL (2011) Challenges of antibacterial discovery. Clin Microbiol Rev 24(1):71–109CrossRefGoogle Scholar
  98. 98.
    Kong KF, Schneper L, Mathee K (2010) Beta-lactam antibiotics: from antibiosis to resistance and bacteriology. APMIS 118(1):1–36CrossRefGoogle Scholar
  99. 99.
    Schneider T, Sahl H-G (2010) An oldie but a goodie–cell wall biosynthesis as antibiotic target pathway. Int J Med Microbiol 300(2–3):161–169CrossRefGoogle Scholar
  100. 100.
    Fuda C, Suvorov M, Vakulenko SB, Mobashery S (2004) The basis for resistance to β-lactam antibiotics by penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus. J Biol Chem 279(39):40802–40806CrossRefGoogle Scholar
  101. 101.
    Hakenbeck R, Brückner R, Denapaite D, Maurer P (2012) Molecular mechanisms of β-lactam resistance in Streptococcus pneumoniae. Future Microbiol 7(3):395–410CrossRefGoogle Scholar
  102. 102.
    Tomberg J, Unemo M, Davies C, Nicholas RA (2010) Molecular and structural analysis of mosaic variants of penicillin-binding protein 2 conferring decreased susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae: role of epistatic mutations. Biochemistry 49(37):8062–8070CrossRefGoogle Scholar
  103. 103.
    Hu Y, Helm JS, Chen L, Ginsberg C, Gross B, Kraybill B, Tiyanont K, Fang X, Wu T, Walker S (2004) Identification of selective inhibitors for the glycosyltransferase MurG via high-throughput screening. Chem Biol 11(5):703–711CrossRefGoogle Scholar
  104. 104.
    Barbosa MD, Ross HO, Hillman MC, Meade RP, Kurilla MG, Pompliano DL (2002) A multitarget assay for inhibitors of membrane-associated steps of peptidoglycan biosynthesis. Anal Biochem 306(1):17–22CrossRefGoogle Scholar
  105. 105.
    Branstrom AA, Midha S, Longley CB, Han K, Baizman ER, Axelrod HR (2000) Assay for identification of inhibitors for bacterial MraY translocase or MurG transferase. Anal Biochem 280(2):315–319CrossRefGoogle Scholar
  106. 106.
    Hrast M, Sosič I, Šink R, Gobec S (2014) Inhibitors of the peptidoglycan biosynthesis enzymes MurA-F. Bioorg Chem 55:2–15CrossRefGoogle Scholar
  107. 107.
    Norris V, Den Blaauwen T, Cabin-Flaman A, Doi RH, Harshey R, Janniere L, Jimenez-Sanchez A, Jin DJ, Levin PA, Mileykovskaya E (2007) Functional taxonomy of bacterial hyperstructures. Microbiol Mol Biol Rev 71 (1):230–253Google Scholar
  108. 108.
    Roos C, Zocher M, Müller D, Münch D, Schneider T, Sahl H-G, Scholz F, Wachtveitl J, Ma Y, Proverbio D (2012) Characterization of co-translationally formed nanodisc complexes with small multidrug transporters, proteorhodopsin and with the E. coli MraY translocase. Biochimica et Biophysica Acta (BBA)-Biomembr 1818(12):3098–3106Google Scholar
  109. 109.
    Ma Y, Münch D, Schneider T, Sahl H-G, Bouhss A, Ghoshdastider U, Wang J, Dötsch V, Wang X, Bernhard F (2011) Preparative scale cell-free production and quality optimization of MraY homologues in different expression modes. J Biol Chem 286(45):38844–38853CrossRefGoogle Scholar
  110. 110.
    Al-Dabbagh B, Henry X, Ghachi ME, Auger G, Blanot D, Parquet C, Mengin-Lecreulx D, Bouhss A (2008) Active site mapping of MraY, a member of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily, catalyzing the first membrane step of peptidoglycan biosynthesis. Biochemistry 47(34):8919–8928CrossRefGoogle Scholar
  111. 111.
    Bouhss A, Crouvoisier M, Blanot D, Mengin-Lecreulx D (2004) Purification and characterization of the bacterial MraY translocase catalyzing the first membrane step of peptidoglycan biosynthesis. J Biol Chem 279(29):29974–29980CrossRefGoogle Scholar
  112. 112.
    Shapiro AB, Jahić H, Gao N, Hajec L, Rivin O (2012) A high-throughput, homogeneous, fluorescence resonance energy transfer-based assay for phospho-N-acetylmuramoyl-pentapeptide translocase (MraY). J Biomol Screen 17(5):662–672CrossRefGoogle Scholar
  113. 113.
    Bernhardt TG, Struck DK, Young R (2001) The lysis protein E of φX174 is a specific inhibitor of the MraY-catalyzed step in peptidoglycan synthesis. J Biol Chem 276(9):6093–6097CrossRefGoogle Scholar
  114. 114.
    Tanaka S, Clemons WM Jr (2012) Minimal requirements for inhibition of MraY by lysis protein E from bacteriophage ΦX174. Mol Microbiol 85(5):975–985CrossRefGoogle Scholar
  115. 115.
    Winn M, Goss RJ, Kimura K-i, Bugg TD (2010) Antimicrobial nucleoside antibiotics targeting cell wall assembly: Recent advances in structure–function studies and nucleoside biosynthesis. Nat Prod Rep 27(2):279–304CrossRefGoogle Scholar
  116. 116.
    Walsh CT, Zhang W (2011) Chemical logic and enzymatic machinery for biological assembly of peptidyl nucleoside antibiotics. ACS PublicationsGoogle Scholar
  117. 117.
    Tanino T, Al-Dabbagh B, Mengin-Lecreulx D, Bouhss A, Oyama H, Ichikawa S, Matsuda A (2011) Mechanistic analysis of muraymycin analogues: a guide to the design of MraY inhibitors. J Med Chem 54(24):8421–8439CrossRefGoogle Scholar
  118. 118.
    Mihalyi A, Jamshidi S, Slikas J, Bugg TD (2014) Identification of novel inhibitors of phospho-MurNAc-pentapeptide translocase MraY from library screening: isoquinoline alkaloid michellamine B and xanthene dye phloxine B. Bioorg Med Chem 22(17):4566–4571CrossRefGoogle Scholar
  119. 119.
    Chung BC, Zhao J, Gillespie RA, Kwon D-Y, Guan Z, Hong J, Zhou P, Lee S-Y (2013) Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis. Science 341(6149):1012–1016CrossRefGoogle Scholar
  120. 120.
    White CL, Kitich A, Gober JW (2010) Positioning cell wall synthetic complexes by the bacterial morphogenetic proteins MreB and MreD. Mol Microbiol 76(3):616–633CrossRefGoogle Scholar
  121. 121.
    Ha S, Walker D, Shi Y, Walker S (2000) The 1.9 Å crystal structure of Escherichia coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis. Protein Sc 9(6):1045–1052Google Scholar
  122. 122.
    Hu Y, Chen L, Ha S, Gross B, Falcone B, Walker D, Mokhtarzadeh M, Walker S (2003) Crystal structure of the MurG: UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases. Proc Natl Acad Sci 100(3):845–849CrossRefGoogle Scholar
  123. 123.
    Brown K, CM Vial S, Dedi N, Westcott J, Scally S, DH Bugg T, A Charlton P, MT Cheetham G (2013) Crystal structure of the Pseudomonas aeruginosa MurG: UDP-GlcNAc substrate complex. Protein Peptide Lett 20(9):1002–1008Google Scholar
  124. 124.
    Crouvoisier M, Auger G, Blanot D, Mengin-Lecreulx D (2007) Role of the amino acid invariants in the active site of MurG as evaluated by site-directed mutagenesis. Biochimie 89(12):1498–1508CrossRefGoogle Scholar
  125. 125.
    Teo AC, Roper DI (2015) Core steps of membrane-bound peptidoglycan biosynthesis: recent advances, insight and opportunities. Antibiotics 4(4):495–520CrossRefGoogle Scholar
  126. 126.
    Trunkfield AE, Gurcha SS, Besra GS, Bugg TD (2010) Inhibition of Escherichia coli glycosyltransferase MurG and Mycobacterium tuberculosis Gal transferase by uridine-linked transition state mimics. Bioorg Med Chem 18(7):2651–2663CrossRefGoogle Scholar
  127. 127.
    Mann PA, Müller A, Xiao L, Pereira PM, Yang C, Ho Lee S, Wang H, Trzeciak J, Schneeweis J, dos Santos MM (2013) Murgocil is a highly bioactive staphylococcal-specific inhibitor of the peptidoglycan glycosyltransferase enzyme MurG. ACS Chem Biol 8(11):2442–2451CrossRefGoogle Scholar
  128. 128.
    Born P, Breukink E, Vollmer W (2006) In vitro synthesis of cross-linked murein and its attachment to sacculi by PBP1A from Escherichia coli. J Biol Chem 281(37):26985–26993CrossRefGoogle Scholar
  129. 129.
    Goffin C, Ghuysen J-M (1998) Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol Mol Biol Rev 62(4):1079–1093CrossRefGoogle Scholar
  130. 130.
    Nguyen-Distèche M, Ayala J (2008) Morphogenesis of rod-shaped sacculi. FEMS Microbiol Rev 32(2):321–344CrossRefGoogle Scholar
  131. 131.
    Zapun A, Vernet T, Pinho MG (2008) The different shapes of cocci. FEMS Microbiol Rev 32(2):345–360CrossRefGoogle Scholar
  132. 132.
    Meberg BM, Sailer FC, Nelson DE, Young KD (2001) Reconstruction of Escherichia coli mrcA (PBP 1a) mutants lacking multiple combinations of penicillin binding proteins. J Bacteriol 183(20):6148–6149CrossRefGoogle Scholar
  133. 133.
    Stefanova ME, Tomberg J, Davies C, Nicholas RA, Gutheil WG (2004) Overexpression and enzymatic characterization of Neisseria gonorrhoeae penicillin-binding protein 4. Eur J Biochem 271(1):23–32CrossRefGoogle Scholar
  134. 134.
    Scheffers D-J, Errington J (2004) PBP1 is a component of the Bacillus subtilis cell division machinery. J Bacteriol 186(15):5153–5156CrossRefGoogle Scholar
  135. 135.
    Pereira S, Henriques A, Pinho M, De Lencastre H, Tomasz A (2007) Role of PBP1 in cell division of Staphylococcus aureus. J Bacteriol 189(9):3525–3531CrossRefGoogle Scholar
  136. 136.
    Zapun A, Contreras-Martel C, Vernet T (2008) Penicillin-binding proteins and β-lactam resistance. FEMS Microbiol Rev 32(2):361–385CrossRefGoogle Scholar
  137. 137.
    Tipper DJ, Strominger JL (1965) Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-d-alanyl-d-alanine. Proc Natl Acad Sci USA 54(4):1133CrossRefGoogle Scholar
  138. 138.
    Hujer AM, Kania M, Gerken T, Anderson VE, Buynak JD, Ge X, Caspers P, Page MG, Rice LB, Bonomo RA (2005) Structure-activity relationships of different β-lactam antibiotics against a soluble form of Enterococcus faecium PBP5, a type II bacterial transpeptidase. Antimicrob Agents Chemother 49(2):612–618CrossRefGoogle Scholar
  139. 139.
    Stefanova ME, Tomberg J, Olesky M, Höltje J-V, Gutheil WG, Nicholas RA (2003) Neisseria gonorrhoeae penicillin-binding protein 3 exhibits exceptionally high carboxypeptidase and β-lactam binding activities. Biochemistry 42(49):14614–14625CrossRefGoogle Scholar
  140. 140.
    Lim D, Strynadka NC (2002) Structural basis for the β-lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat Struct Mol Biol 9(11):870Google Scholar
  141. 141.
    Konaklieva MI (2014) Molecular targets of β-lactam-based antimicrobials: beyond the usual suspects. Antibiotics 3(2):128–142CrossRefGoogle Scholar
  142. 142.
    Guinane CM, Cotter PD, Ross RP, Hill C (2006) Contribution of penicillin-binding protein homologs to antibiotic resistance, cell morphology, and virulence of Listeria monocytogenes EGDe. Antimicrob Agents Chemother 50(8):2824–2828CrossRefGoogle Scholar
  143. 143.
    Macheboeuf P, Fischer DS, Brown T Jr, Zervosen A, Luxen A, Joris B, Dessen A, Schofield CJ (2007) Structural and mechanistic basis of penicillin-binding protein inhibition by lactivicins. Nat Chem Biol 3(9):565CrossRefGoogle Scholar
  144. 144.
    Brown T Jr, Charlier P, Herman R, Schofield CJ, Sauvage E (2010) Structural basis for the interaction of lactivicins with serine β-lactamases. J Med Chem 53(15):5890–5894CrossRefGoogle Scholar
  145. 145.
    Zervosen A, Sauvage E, Frère J-M, Charlier P, Luxen A (2012) Development of new drugs for an old target—the penicillin binding proteins. Molecules 17(11):12478–12505CrossRefGoogle Scholar
  146. 146.
    Atkinson S, Williams P (2009) Quorum sensing and social networking in the microbial world. J R Soc Interface 6(40):959–978CrossRefGoogle Scholar
  147. 147.
    Hentzer M, Wu H, Andersen JB, Riedel K, Rasmussen TB, Bagge N, Kumar N, Schembri MA, Song Z, Kristoffersen P (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22(15):3803–3815CrossRefGoogle Scholar
  148. 148.
    Cheung GY, Wang R, Khan BA, Sturdevant DE, Otto M (2011) Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect Immun 79(5):1927–1935CrossRefGoogle Scholar
  149. 149.
    Zhu L, Lau GW (2011) Inhibition of competence development, horizontal gene transfer and virulence in Streptococcus pneumoniae by a modified competence stimulating peptide. PLoS Pathog 7(9):e1002241CrossRefGoogle Scholar
  150. 150.
    Rasko DA, Sperandio V (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat Rev Drug Discov 9(2):117CrossRefGoogle Scholar
  151. 151.
    Christensen QH, Grove TL, Booker SJ, Greenberg EP (2013) A high-throughput screen for quorum-sensing inhibitors that target acyl-homoserine lactone synthases. Proc Natl Acad Sci 110(34):13815–13820CrossRefGoogle Scholar
  152. 152.
    Chun CK, Ozer EA, Welsh MJ, Zabner J, Greenberg E (2004) Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia. Proc Natl Acad Sci 101(10):3587–3590CrossRefGoogle Scholar
  153. 153.
    Hong K-W, Koh C-L, Sam C-K, Yin W-F, Chan K-G (2012) Quorum quenching revisited—from signal decays to signalling confusion. Sensors 12(4):4661–4696CrossRefGoogle Scholar
  154. 154.
    Dong Y-H, Wang L-H, Xu J-L, Zhang H-B, Zhang X-F, Zhang L-H (2001) Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature 411(6839):813CrossRefGoogle Scholar
  155. 155.
    Mattmann ME, Shipway PM, Heth NJ, Blackwell HE (2011) Potent and selective synthetic modulators of a quorum sensing repressor in Pseudomonas aeruginosa identified from second-generation libraries of N-acylated l-homoserine lactones. Chem Bio Chem 12(6):942–949CrossRefGoogle Scholar
  156. 156.
    O’Loughlin CT, Miller LC, Siryaporn A, Drescher K, Semmelhack MF, Bassler BL (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci 110(44):17981–17986CrossRefGoogle Scholar
  157. 157.
    Heeb S, Fletcher MP, Chhabra SR, Diggle SP, Williams P, Cámara M (2011) Quinolones: from antibiotics to autoinducers. FEMS Microbiol Rev 35(2):247–274CrossRefGoogle Scholar
  158. 158.
    Lee J, Wu J, Deng Y, Wang J, Wang C, Wang J, Chang C, Dong Y, Williams P, Zhang L-H (2013) A cell-cell communication signal integrates quorum sensing and stress response. Nat Chem Biol 9(5):339CrossRefGoogle Scholar
  159. 159.
    Dulcey CE, Dekimpe V, Fauvelle D-A, Milot S, Groleau M-C, Doucet N, Rahme LG, Lépine F, Déziel E (2013) The end of an old hypothesis: the Pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids. Chem Biol 20(12):1481–1491CrossRefGoogle Scholar
  160. 160.
    Bera AK, Atanasova V, Robinson H, Eisenstein E, Coleman JP, Pesci EC, Parsons JF (2009) Structure of PqsD, a Pseudomonas quinolone signal biosynthetic enzyme, in complex with anthranilate. Biochemistry 48(36):8644–8655CrossRefGoogle Scholar
  161. 161.
    Weidel E, de Jong JC, Brengel C, Storz MP, Braunshausen A, Negri M, Plaza A, Steinbach A, Müller R, Hartmann RW (2013) Structure optimization of 2-benzamidobenzoic acids as PqsD inhibitors for Pseudomonas aeruginosa infections and elucidation of binding mode by SPR, STD NMR, and molecular docking. J Med Chem 56(15):6146–6155CrossRefGoogle Scholar
  162. 162.
    Pustelny C, Albers A, Büldt-Karentzopoulos K, Parschat K, Chhabra SR, Cámara M, Williams P, Fetzner S (2009) Dioxygenase-mediated quenching of quinolone-dependent quorum sensing in Pseudomonas aeruginosa. Chem Biol 16(12):1259–1267CrossRefGoogle Scholar
  163. 163.
    LaSarre B, Federle MJ (2013) Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev 77(1):73–111CrossRefGoogle Scholar
  164. 164.
    Thoendel M, Kavanaugh JS, Flack CE, Horswill AR (2010) Peptide signaling in the staphylococci. Chem Rev 111(1):117–151CrossRefGoogle Scholar
  165. 165.
    Gordon CP, Williams P, Chan WC (2013) Attenuating Staphylococcus aureus virulence gene regulation: a medicinal chemistry perspective. J Med Chem 56(4):1389–1404CrossRefGoogle Scholar
  166. 166.
    Peterson MM, Mack JL, Hall PR, Alsup AA, Alexander SM, Sully EK, Sawires YS, Cheung AL, Otto M, Gresham HD (2008) Apolipoprotein B is an innate barrier against invasive Staphylococcus aureus infection. Cell Host Microbe 4(6):555–566CrossRefGoogle Scholar
  167. 167.
    Park J, Jagasia R, Kaufmann GF, Mathison JC, Ruiz DI, Moss JA, Meijler MM, Ulevitch RJ, Janda KD (2007) Infection control by antibody disruption of bacterial quorum sensing signaling. Chem Biol 14(10):1119–1127CrossRefGoogle Scholar
  168. 168.
    Nakayama J, Uemura Y, Nishiguchi K, Yoshimura N, Igarashi Y, Sonomoto K (2009) Ambuic acid inhibits the biosynthesis of cyclic peptide quormones in gram-positive bacteria. Antimicrob Agents Chemother 53(2):580–586CrossRefGoogle Scholar
  169. 169.
    Lyon GJ, Wright JS, Muir TW, Novick RP (2002) Key determinants of receptor activation in the agr autoinducing peptides of Staphylococcus aureus. Biochemistry 41(31):10095–10104CrossRefGoogle Scholar
  170. 170.
    Nakayama J, Yokohata R, Sato M, Suzuki T, Matsufuji T, Nishiguchi K, Kawai T, Yamanaka Y, Nagata K, Tanokura M (2013) Development of a peptide antagonist against fsr quorum sensing of Enterococcus faecalis. ACS Chem Biol 8(4):804–811CrossRefGoogle Scholar
  171. 171.
    Jessen DL, Bradley DS, Nilles ML (2014) A type III secretion system inhibitor targets YopD while revealing differential regulation of secretion in calcium-blind mutants of Yersinia pestis. Antimicrob Agents Chemother 58(2):839–850CrossRefGoogle Scholar
  172. 172.
    Heidenreich O (2003) RNA siRNAs: magic bullets for functional genomics and therapy? Eur Pharm Rev 8(4):19–28Google Scholar
  173. 173.
    Then R (2004) Antimicrobial dihydrofolate reductase inhibitors-achievements and future options. J Chemother 16(1):3–12CrossRefGoogle Scholar
  174. 174.
    Ng V, Chan WC (2016) New found hope for antibiotic discovery: lipid II inhibitors. Chem Eur J 22(36):12606–12616Google Scholar
  175. 175.
    Healy VL, Lessard IA, Roper DI, Knox JR, Walsh CT (2000) Vancomycin resistance in enterococci: reprogramming of the d-Ala–d-Ala ligases in bacterial peptidoglycan biosynthesis. Chem Biol 7(5):R109–R119CrossRefGoogle Scholar
  176. 176.
    Percy MG, Gründling A (2014) Lipoteichoic acid synthesis and function in gram-positive bacteria. Annu Rev Microbiol 68:81–100CrossRefGoogle Scholar
  177. 177.
    Wecke J, Perego M, Fischer W (1996) d-alanine deprivation of Bacillus subtilis teichoic acids is without effect on cell growth and morphology but affects the autolytic activity. Microbial Drug Resist 2(1):123–129CrossRefGoogle Scholar
  178. 178.
    Kristian SA, Datta V, Weidenmaier C, Kansal R, Fedtke I, Peschel A, Gallo RL, Nizet V (2005) d-alanylation of teichoic acids promotes group a streptococcus antimicrobial peptide resistance, neutrophil survival, and epithelial cell invasion. J Bacteriol 187(19):6719–6725CrossRefGoogle Scholar
  179. 179.
    Walter J, Loach DM, Alqumber M, Rockel C, Hermann C, Pfitzenmaier M, Tannock GW (2007) d-Alanyl ester depletion of teichoic acids in Lactobacillus reuteri 100-23 results in impaired colonization of the mouse gastrointestinal tract. Environ Microbiol 9(7):1750–1760CrossRefGoogle Scholar
  180. 180.
    May JJ, Finking R, Wiegeshoff F, Weber TT, Bandur N, Koert U, Marahiel MA (2005) Inhibition of the d-alanine: d-alanyl carrier protein ligase from Bacillus subtilis increases the bacterium’s susceptibility to antibiotics that target the cell wall. FEBS J 272(12):2993–3003CrossRefGoogle Scholar
  181. 181.
    McBride SM, Sonenshein AL (2011) The dlt operon confers resistance to cationic antimicrobial peptides in Clostridium difficile. Microbiology 157(5):1457–1465CrossRefGoogle Scholar
  182. 182.
    Perego M, Glaser P, Minutello A, Strauch MA, Leopold K, Fischer W (1995) Incorporation of d-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis identification of genes and regulation. J Biol Chem 270(26):15598–15606CrossRefGoogle Scholar
  183. 183.
    Abou-Dobara MI, Omar NF, Diab MA, El-Sonbati AZ, Morgan SM, El-Mogazy MA (2019) Allyl rhodanine azo dye derivatives: Potential antimicrobials target d-alanyl carrier protein ligase and nucleoside diphosphate kinase. J Cell Biochem 120(2):1667–1678CrossRefGoogle Scholar
  184. 184.
    Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4(4):406–425Google Scholar
  185. 185.
    Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39(4):783–791CrossRefGoogle Scholar
  186. 186.
    Zuckerkandl E, Pauling L (1965) Evolutionary divergence and convergence in proteins. In: Evolving genes and proteins. Elsevier, pp 97–166Google Scholar
  187. 187.
    Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24(8):1596–1599Google Scholar
  188. 188.
    Du L, He Y, Luo Y (2008) Crystal structure and enantiomer selection by d-alanyl carrier protein ligase DltA from Bacillus cereus. Biochemistry 47(44):11473–11480CrossRefGoogle Scholar
  189. 189.
    Osman KT, Du L, He Y, Luo Y (2009) Crystal Structure of Bacillus cereus d-Alanyl Carrier Protein Ligase (DltA) in Complex with ATP. J Mol Biol 388(2):345–355CrossRefGoogle Scholar
  190. 190.
    Reichmann NT, Cassona CP, Gründling A (2013) Revised mechanism of d-alanine incorporation into cell wall polymers in Gram-positive bacteria. Microbiology 159(9):1868–1877CrossRefGoogle Scholar
  191. 191.
    Stuible H-P, Büttner D, Ehlting J, Hahlbrock K, Kombrink E (2000) Mutational analysis of 4-coumarate: CoA ligase identifies functionally important amino acids and verifies its close relationship to other adenylate-forming enzymes. FEBS Lett 467(1):117–122CrossRefGoogle Scholar
  192. 192.
    Yonus H, Neumann P, Zimmermann S, May JJ, Marahiel MA, Stubbs MT (2008) Crystal structure of DltA implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains. J Biol Chem 283(47):32484–32491CrossRefGoogle Scholar
  193. 193.
    Gwynn MN, Portnoy A, Rittenhouse SF, Payne DJ (2010) Challenges of antibacterial discovery revisited. Ann NY Acad Sci 1213(1):5–19CrossRefGoogle Scholar
  194. 194.
    Altschul SF, Wootton JC, Gertz EM, Agarwala R, Morgulis A, Schäffer AA, Yu YK (2005) Protein database searches using compositionally adjusted substitution matrices. FEBS J 272(20):5101–5109CrossRefGoogle Scholar
  195. 195.
    Crooks GE, Hon G, Chandonia J-M, Brenner SE (2004) WebLogo: a sequence logo generator. Genome Res 14(6):1188–1190CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Botany and Microbiology Department, Faculty of ScienceDamietta UniversityDamiettaEgypt

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