Murgocil is a highly bioactive staphylococcal-specific inhibitor of the peptidoglycan glycosyltransferase enzyme MurG

ACS Chemical Biology

Volumn 8, Issue 11, 2013, Pages 2442-2451

  Mann, Paul A ^a   Müller, Anna ^b   Xiao, Li ^a   Pereira, Pedro M ^c   Yang, Christine ^a   Ho Lee, Sang ^a   Wang, Hao ^a   Trzeciak, Joanna ^a   Schneeweis, Jonathan ^a   Dos Santos, Margarida Moreira ^c   Murgolo, Nicholas ^a   She, Xinwei ^a   Gill, Charles ^a   Balibar, Carl J ^a   Labroli, Marc ^a   Su, Jing ^a   Flattery, Amy ^a   Sherborne, Brad ^a   Maier, Richard ^d,e   Tan, Christopher M ^a   Black, Todd ^a   Önder, Kamil ^d,e   Kargman, Stacia ^a   Monsma, Frederick J ^a   Pinho, Mariana G ^c   Schneider, Tanja ^b,f   Roemer, Terry ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

^b UNIVERSITY OF BONN   (Germany)

^c INSTITUTO DE TECNOLOGIA QUÍMICA E BIOLÓGICA   (Portugal)

^d Procomcure Biotech GmbH   (Austria)

^e PARACELSUS MEDICAL UNIVERSITY   (Austria)

^f UNIVERSITY OF COLOGNE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERICIDE; BAMBERMYCIN; BETA LACTAM DERIVATIVE; ERTAPENEM; GLYCOSYLTRANSFERASE INHIBITOR; IMIPENEM; MURGOCIL; PENICILLIN BINDING PROTEIN; PEPTIDOGLYCAN GLYCOSYLTRANSFERASE; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE N ACETYLGLUCOSAMINE; VANCOMYCIN; ANTIINFECTIVE AGENT; ENZYME INHIBITOR; N ACETYLGLUCOSAMINYLTRANSFERASE; OUTER MEMBRANE PROTEIN; PYRAZOLE DERIVATIVE; STEROL; UDP-N-ACETYLGLUCOSAMINE-N-ACETYLMURAMYL-(PENTAPEPTIDE)PYROPHOSPHORYL-UNDECAPRENOL N-ACETYLGLUCOSAMINE TRANSFERASE;

AMINO ACID SUBSTITUTION; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL CELL WALL; BACTERIAL MUTATION; BACTERICIDAL ACTIVITY; BIOGENESIS; CHEMICAL STRUCTURE; CRYSTAL STRUCTURE; DRUG POTENTIATION; ENZYME ACTIVITY; ENZYME SYNTHESIS; GROWTH INHIBITION; IN VITRO STUDY; INTRACELLULAR MEMBRANE; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MINIMUM INHIBITORY CONCENTRATION; MISSENSE MUTATION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN CROSS LINKING; PROTEIN LOCALIZATION; PROTEIN POLYMERIZATION; STAPHYLOCOCCUS; STAPHYLOCOCCUS EPIDERMIDIS; WHOLE CELL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; COMPUTER SIMULATION; DRUG EFFECTS; ENZYMOLOGY; FLUORESCENCE MICROSCOPY; HUMAN; METABOLISM; STAPHYLOCOCCUS AUREUS;

ANTI-BACTERIAL AGENTS; BACTERIAL OUTER MEMBRANE PROTEINS; COMPUTER SIMULATION; DRUG RESISTANCE, BACTERIAL; ENZYME INHIBITORS; HUMANS; MICROSCOPY, FLUORESCENCE; MODELS, MOLECULAR; N-ACETYLGLUCOSAMINYLTRANSFERASES; PEPTIDOGLYCAN GLYCOSYLTRANSFERASE; PYRAZOLES; STAPHYLOCOCCUS AUREUS; STEROLS;

EID: 84887933280     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb400487f     Document Type: Article

References (59)

1. van Heijenoort, J. (2001) Recent advances in the formation of the bacterial peptidoglycan monomer unit Nat. Prod. Rep. 18, 503-519
2. van Heijenoort, J. (2007) Lipid intermediates in the biosynthesis of bacterial peptidoglycan Microbiol. Mol. Biol. Rev. 71, 620-635
3. Scheffers, D. J. and Pinho, M. G. (2005) Bacterial cell wall synthesis: New insights from localization studies Microbiol. Mol. Biol. Rev. 69, 585-607
4. Walsh, C. Antibiotics: Actions, Origins, Resistance (2003) ASM Press, Washington, DC.
5. Klevens, R. M., Morrison, M. A., Nadle, J., Petit, S., Gershman, K., Ray, S., Harrison, L. H., Lynfield, R., Dumyati, G., Townes, J. M., Craig, A. S., Zell, E. R., Fosheim, G. E., McDougal, L. K., Carey, R. B., and Fridkin, S. K. (2007) Active bacterial core surveillance (ABCs) MRSA investigators JAMA 298, 1763-1771
6. Boucher, H. W., Talbot, G. H., Bradley, J. S., Edwards, J. E., Gilbert, D., Rice, L. B., Scheld, M., Spellberg, B., and Bartlett, J. (2009) Bad bugs, no drugs: No ESKAPE! An update from the Infectious Diseases Society of America Clin. Infect. Dis. 48, 1-12
7. Couto, I., de Lencastre, H., Severina, E., Kloos, W., Webster, J. A., Hubner, R. J., Sanches, I. S., and Tomasz, A. (1996) Ubiquitous presence of a mecA homologue in natural isolates of Staphylococcus sciuri Microb. Drug Resist. 2, 377-391
8. de Lencastre, H., Oliveira, D., and Tomasz, A. (2007) Antibiotic resistant Staphylococcus aureus: A paradigm of adaptive power Curr. Opin. Microbiol. 10, 428-435
9. Fuda, C. C., Fisher, J. F., and Mobashery, S. (2005) β-Lactam resistance in Staphylococcus aureus: The adaptive resistance of a plastic genome Cell. Mol. Life Sci. 62, 2617-2633
10. Fuda, C., Suvorov, M., Vakulenko, S. B., and 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, 40802-40806
11. Llarrull, L. I., Fisher, J. F., and Mobashery, S. (2009) Molecular basis and phenotype of methicillin resistance in Staphylococcus aureus and insights into new β-lactams that meet the challenge Antimicrob. Agents Chemother. 53, 4051-4063
12. Pinho, M. G., de Lencastre, H., and Tomasz, A. (2001) An acquired and a native penicillin binding protein cooperate in building the cell wall of drug-resistant staphylococci Proc. Natl. Acad. Sci. U.S.A. 98, 10886-10891
13. Pinho, M. G., Filipe, S. R., de Lencastre, H., and Tomasz, A. (2001) Complementation of the essential peptidoglycan transpeptidase function of penicillin-binding protein 2 (PBP2) by the drug resistance protein PBP2A in Staphylococcus aureus J. Bacteriol. 183, 6525-6531
14. de Lencastre, H. and Tomasz, A. (1994) Reassessment of the number of auxiliary genes essential for expression of high-level methicillin resistance in Staphylococcus aureus Antimicrob. Agents Chemother. 38, 2590-2598
15. de Lencastre, H., Wu, S. W., Pinho, M. G., Ludovice, A. M., Filipe, S., Gardete, S., Sobral, R., Gill, S., Chung, M., and Tomasz, A. (1999) Antibiotic resistance as a stress response: Complete sequencing of a large number of chromosomal loci in Staphylococcus aureus strain COL that impact on the expression of resistance to methicillin Microb. Drug Resist. 5, 163-175
16. Berger-Bächi, B. and Rohrer, S. (2002) Factors influencing methicillin resistance in staphylococci Arch. Microbiol. 178, 165-171
17. Lee, S. H., Wang-Jarantow, L., Wang, H., Sillaots, S., Cheng, H., Meredith, T. C., Thompson, J., and Roemer, T. (2011) Antagonism of chemical genetic interaction networks resensitize MRSA to β-lactam antibiotics Chem. Biol. 18, 1379-1389
18. Roemer, T., Schneider, T., and Pinho, M. G. Accessory factors: A chink in the armor of MRSA resistance to β-lactam antibiotics. Curr. Opin. Microbiol. 2013, in press
19. Huber, J., Donald, R. G., Lee, S. H., Jarantow, L. W., Salvatore, M. J., Meng, X., Painter, R., Onishi, R. H., Occi, J., Dorso, K., Young, K., Park, Y. W., Skwish, S., Szymonifka, M. J., Waddell, T. S., Miesel, L., Phillips, J. W., and Roemer, T. (2009) Chemical genetic identification of peptidoglycan inhibitors potentiating carbapenem activity against methicillin-resistant Staphylococcus aureus Chem. Biol. 16, 837-848
20. Tan, C. M., Therien, A. G., Lu, J., Lee, S. H., Caron, A., Gill, C. J., Lebeau-Jacob, C., Benton-Perdomo, L., Monteiro, J. M., Pereira, P. M., Elsen, N. L., Wu, J., Deschamps, K., Petcu, M., Wong, S., Daigneault, E., Kramer, S., Liang, L., Maxwell, E., Claveau, D., Vaillancourt, J., Skorey, K., Tam, J., Wang, H., Meredith, T. C., Sillaots, S., Wang-Jarantow, L., Ramtohul, Y., Langlois, E., Landry, F., Reid, J. C., Parthasarathy, G., Sharma, S., Baryshnikova, A., Lumb, K. J., Pinho, M. G., Soisson, S. M., and Roemer, T. (2012) Restoring methicillin-resistant Staphylococcus aureus susceptibility to β-lactam antibiotics Sci. Transl. Med. 4, 126ra35
21. Koyama, N., Tokura, Y., Münch, D., Sahl, H. G., Schneider, T., Shibagaki, Y., Ikeda, H., and Tomoda, H. (2012) The nonantibiotic small molecule cyslabdan enhances the potency of β-lactams against MRSA by inhibiting pentaglycine interpeptide bridge synthesis PLoS One 7, e48981
22. Therien, A. G., Huber, J. L., Wilson, K. E., Beaulieu, P., Caron, A., Claveau, D., Deschamps, K., Donald, R. G., Galgoci, A. M., Gallant, M., Gu, X., Kevin, N. J., Lafleur, J., Leavitt, P. S., Lebeau-Jacob, C., Lee, S. S., Lin, M. M., Michels, A. A., Ogawa, A. M., Painter, R. E., Parish, C. A., Park, Y. W., Benton-Perdomo, L., Petcu, M., Phillips, J. W., Powles, M. A., Skorey, K. I., Tam, J., Tan, C. M., Young, K., Wong, S., Waddell, S. T., and Miesel, L. (2012) Broadening the spectrum of β-lactam antibiotics through inhibition of signal peptidase type I Antimicrob. Agents Chemother. 56, 4662-4670
23. Silver, L. L. (2013) Viable screening targets related to the bacterial cell wall Ann. N.Y. Acad. Sci. 277, 29-53
24. Isono, K., Uramoto, M., Kusakabe, H., Kimura, K., Isaki, K., Nelson, C. C., and McCloskey, J. A. (1985) Liposidomycins: Novel nucleoside antibiotics which inhibit bacterial peptidoglycan synthesis J. Antibiot. 38, 1617-1621
25. Kimura, K.-I., Miyata, N., Kawanishi, G., Kamio, Y., Izaki, K., Isono, and K. (1989) Liposidomycin C inhibits phospho-N-acetylmuramyl-pentapeptide transferase in peptidoglycan synthesis of Escherichia coli Y-10 Agric. Biol. Chem. 53, 1811-1815
26. Brandish, P. E., Burnham, M. K., Lonsdale, J. T., Southgate, R., Inukai, M., and Bugg, T. D. (1996) Slow-binding inhibition of phospho-N-acetylmuramyl- pentapeptide translocase (Escherichia coli) by mureidomycin A J. Biol. Chem. 271, 7609-7614
27. Silver, L. L. (2011) Challenges of antibacterial discovery Clin. Microbiol. Rev. 24, 71-109
28. Ha, S., Walker, D., Shi, Y., and Walker, S. (2000) The 1.9 A crystal structure of Escherichia coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis Protein Sci. 9, 1045-1052
29. Hu, Y., Chen, L., Ha, S., Gross, B., Falcone, B., Walker, D., Mokhtarzadeh, M., and Walker, S. (2003) Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases Proc. Natl. Acad. Sci. U.S.A. 100, 845-849
30. Campbell, J., Singh, A. K., Santa Maria, J. P., Kim, Y., Brown, S., Swoboda, J. G., Mylonakis, E., Wilkinson, B., and Walker, S. (2011) Synthetic lethal compound combinations reveal a fundamental connection between wall teichoic acid and peptidoglycan biosyntheses in Staphylococcus aureus ACS Chem. Biol. 6, 106-116
31. Brown, S., Xia, G., Luhachack, L. G., Campbell, J., Meredith, T. C., Chen, C., Winstel, V., Gekeler, C., Irazoqui, J. E., Peschel, A., and Walker, S. (2012) Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids Proc. Natl. Acad. Sci. U.S.A. 109, 18909-18914
32. Weidenmaier, C. and Peschel, A. (2008) Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions Nat. Rev. Microbiol. 6, 276-287
33. Swoboda, J. G., Campbell, J., Meredith, T. C., and Walker, S. (2010) Wall teichoic acid function, biosynthesis, and inhibition ChemBioChem 11, 35-45
34. Meredith, T. C., Wang, H., Beaulieu, P., Gründling, A., and Roemer, T. (2012) Harnessing the power of transposon mutagenesis for antibacterial target identification and evaluation Mobil Genet. Elem. 2, 171-178
35. Farha, M. A., Leung, A., Sewell, E. W., D'Elia, M. A., Allison, S. E., Ejim, L., Pereira, P. M., Pinho, M. G., Wright, G. D., and Brown, E. D. (2013) Inhibition of WTA synthesis blocks the cooperative action of PBPs and sensitizes MRSA to β-lactams ACS Chem. Biol. 8, 226-233
36. Donald, R. G., Skwish, S., Forsyth, R. A., Anderson, J. W., Zhong, T., Burns, C., Lee, S., Meng, X., LoCastro, L., Jarantow, L. W., Martin, J., Lee, S. H., Taylor, I., Robbins, D., Malone, C., Wang, L., Zamudio, C. S., Youngman, P. J., and Phillips, J. W. (2009) A Staphylococcus aureus fitness test platform for mechanism-based profiling of antibacterial compounds Chem. Biol. 16, 826-836
37. Wang, H., Gill, C. J., Lee, S. H., Mann, P., Zuck, P., Meredith, T. C., Murgolo, N., She, X., Kales, S., Liang, L., Liu, J., Wu, J., Santa Maria, J., Su, J., Pan, J., Hailey, J., Mcguinness, D., Tan, C. M., Flattery, A., Walker, S., Black, T., and Roemer, T. (2013) Discovery of novel wall teichoic acid inhibitors as effective anti-MRSA β-lactam combination agents Chem. Biol. 20, 272-284
38. Schneider, T., Kruse, T., Wimmer, R., Wiedemann, I., Sass, V., Pag, U., Jansen, A., Nielsen, A. K., Mygind, P. H., Raventós, D. S., Neve, S., Ravn, B., Bonvin, A. M., De Maria, L., Andersen, A. S., Gammelgaard, L. K., Sahl, H. G., and Kristensen, H. H. (2010) Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II Science 328, 1168-1172
39. Pinho, M. G. and Errington, J. (2005) Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates Mol. Microbiol. 55, 799-807
40. Adams, D. W. and Errington, J. (2009) Bacterial cell division: Assembly, maintenance, and disassembly of the Z ring Nat. Rev. Microbiol. 7, 642-653
41. Pinho, M. G. and Errington, J. (2003) Dispersed mode of Staphylococcus aureus cell wall synthesis in the absence of the division machinery Mol. Microbiol. 50, 871-881
42. Jorge, A. M., Hoiczyk, E., Gomes, J. P., and Pinho, M. G. (2011) EzrA contributes to the regulation of cell size in Staphylococcus aureus PLoS One 6, e27542
43. Silver, L. L. (2003) Novel inhibitors of bacterial cell wall synthesis Curr. Opin. Microbiol. 6, 431-438
44. Payne, D. J., Gwynn, M. N., Holmes, D. J., and Pompliano, D. L. (2007) Drugs for bad bugs: Confronting the challenges of antibacterial discovery Nat. Rev. Drug Discov. 6, 29-40
45. Hu, Y., Helm, J. S., Chen, L., Ye, X. Y., and Walker, S. (2003) Ramoplanin inhibits bacterial transglycosylases by binding as a dimer to lipid II J. Am. Chem. Soc. 125, 8736-8737
46. Silver, L. L. (2006) Does the cell wall of bacteria remain a viable source of targets for novel antibiotics? Biochem. Pharmacol. 71, 996-1005
47. Schneider, T., Gries, K., Josten, M., Wiedemann, I., Pelzer, S., Labischinski, H., and Sahl, H. G. (2009) The lipopeptide antibiotic Friulimicin B inhibits cell wall biosynthesis through complex formation with bactoprenol phosphate Antimicrob. Agents Chemother. 53, 1610-1618
48. Helm, J. S., Hu, Y., Chen, L., Gross, B., and Walker, S. (2003) Identification of active-site inhibitors of MurG using a generalizable, high-throughput glycosyltransferase screen J. Am. Chem. Soc. 125, 11168-11169
49. Hu, Y., Helm, J. S., Chen, L., Ginsberg, C., Gross, B., Kraybill, B., Tiyanont, K., Fang, X., Wu, T., and Walker, S. (2004) Identification of selective inhibitors for the glycosyltransferase MurG via high-throughput screening Chem. Biol. 11, 703-711
50. Barbosa, M. D., Ross, H. O., Hillman, M. C., Meade, R. P., Kurilla, M. G., and Pompliano, D. L. (2002) A multitarget assay for inhibitors of membrane-associated steps of peptidoglycan biosynthesis Anal. Biochem. 306, 17-22
51. Barbosa, M. D., Yang, G., Fang, J., Kurilla, M. G., and Pompliano, D. L. (2002) Development of a whole-cell assay for peptidoglycan biosynthesis inhibitors Antimicrob. Agents Chemother. 46, 943-946
52. DeCenzo, M., Kuranda, M., Cohen, S., Babiak, J., Jiang, Z. D., Su, D., Hickey, M., Sancheti, P., Bradford, P. A., Youngman, P., Projan, S., and Rothstein, D. M. (2002) Identification of compounds that inhibit late steps of peptidoglycan synthesis in bacteria J. Antibiot. 55, 288-295
53. Foss, M. H., Eun, Y. J., and Weibel, D. B. (2011) Chemical-biological studies of subcellular organization in bacteria Biochemistry 50, 7719-7734
54. Rubinchik, E., Schneider, T., Elliott, M., Scott, W. R., Pan, J., Anklin, C., Yang, H., Dugourd, D., Müller, A., Gries, K., Straus, S. K., Sahl, H. G., and Hancock, R. E. (2011) Mechanism of Action and limited cross-resistance of new lipopeptide MX-2401 Antimicrob. Agents Chemother. 55, 2743-2754
55. Schneider, T., Senn, M. M., Berger-Bächi, B., Tossi, A., Sahl, H. G., and Wiedemann, I. (2004) In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus Mol. Microbiol. 53, 675-685
56. LigPrep Glide, Macromodel (2012) Schrödinger, LLC, New York.
57. MOE, Molecular Operating Environment, 2012.10 (2012) Chemical Computing Group Inc., Montreal, QC, Canada.
58. Abràmoff, M. D., Magalhães, P. J., and Ram, S. J. (2004) Image processing with ImageJ Biophotonics Int. 11, 36-42
59. Pereira, P. M., Filipe, S. R., Tomasz, A., and Pinho, M. G. (2007) Fluorescence ratio imaging microscopy shows decreased access of vancomycin to cell wall synthetic sites in vancomycin-resistant Staphylococcus aureus Antimicrob. Agents Chemother. 51, 3627-3633