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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Potential of MurA Enzyme and GBAP in Fsr Quorum Sensing System as Antibacterial Drugs Target: In vitro and In silico Study of Antibacterial Compounds from Myrmecodia pendans

Author(s): Eti Apriyanti, Mieke H. Satari and Dikdik Kurnia*

Volume 24 , Issue 1 , 2021

Published on: 28 June, 2020

Page: [109 - 118] Pages: 10

DOI: 10.2174/1386207323666200628111348

open access plus

Abstract

Background: Increasing the resistance issue has become the reason for the development of new antibacterial in crucial condition. Many ways are tracked to determine the most effective antibacterial agent. Some proteins that are a key role in bacteria metabolism are targeted, including MurA in cell wall biosynthesis and gelatinase biosynthesis-activating pheromone (GBAP) in Fsr Quorum Sensing (QS) system.

Objective: The objective of this research is the analysis of compounds 1-4 from M. pendans as antibacterial and anti-QS activity trough protein inhibition by in silico study; focus on the structure-activity relationships, to appraise their role as an antibacterial and anti-QS agent in the molecular level.

Methods: Both activities of M. pendans compounds (1-4) were analyzed by in silico, compared to Fosfomycin, Ambuic acid, Quercetin, and Taxifolin as a standard. Chemical structures of M. pendans compounds were converted using an online program molview. The compounds were docked to MurA, GBAP, gelatinase and serine protease using Autodock Vina in Pyrx 0.8 followed PYMOL to visualization and proteis.plus program to analyze of the complex.

Results: All compounds from M. pendans bound on MurA, GBAP, gelatinase and serine protease except compound 2. This biflavonoid did not attach to MurA and serine protease yet is the favorable ligand for GBAP and gelatinase with the binding affinity of -6.9 and -9.4 Kcal/mol respectively. Meanwhile, for MurA and serine protease, compound 4 is the highest of bonding energy with values of -8.7 and -6.4 Kcal/mol before quercetin (MurA, -8.9 Kcal/mol) and taxifolin (serine protease, -6.6 Kcal/mol).

Conclusion: Based on the data, biflavonoid acts better as anti-QS than an inhibitor of MurA enzyme while the others can be acted into both of them either the therapeutic agent of anti-QS or antibacterial agent of MurA inhibitor.

Keywords: Quorum sensing, in silico, GBAP, Gelatinase, Serine protease, MurA, Flavonoid, M. pendans.

[1]
Aslam, B.; Wang, W.; Arshad, M.I.; Khurshid, M.; Muzammil, S.; Rasool, M.H.; Nisar, M.A.; Alvi, R.F.; Aslam, M.A.; Qamar, M.U.; Salamat, M.K.F.; Baloch, Z. Antibiotic resistance: a rundown of a global crisis. Infect. Drug Resist., 2018, 11, 1645-1658.
[http://dx.doi.org/10.2147/IDR.S173867] [PMID: 30349322]
[2]
Walsh, C.T.; Wencewicz, T.A. Prospects for new antibiotics: a molecule-centered perspective. J. Antibiot. (Tokyo), 2014, 67(1), 7-22.
[http://dx.doi.org/10.1038/ja.2013.49] [PMID: 23756684]
[3]
Skarzynski, T.; Mistry, A.; Wonacott, A.; Hutchinson, S.E.; Kelly, V.A.; Duncan, K. Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin. Structure, 1996, 4(12), 1465-1474.
[http://dx.doi.org/10.1016/S0969-2126(96)00153-0] [PMID: 8994972]
[4]
Deepak, S.M.; Patil, P.P.; Aher, S.J.; Ware, A.L. MUR-A: A critical target behind new antibacterial drug discovery. Indo Am. J. Pharm., 2014, 4(1), 220-225.
[5]
Sapkota, M.; Marreddy, R.K.R.; Wu, X.; Kumar, M.; Hurdle, J.G. The early stage peptidoglycan biosynthesis Mur enzymes are antibacterial and antisporulation drug targets for recurrent Clostridioides difficile infection. Anaerobe, 2020, 61102129
[http://dx.doi.org/10.1016/j.anaerobe.2019.102129] [PMID: 31760080]
[6]
Reading, N.C.; Sperandio, V. Quorum sensing: the many languages of bacteria. FEMS Microbiol. Lett., 2006, 254(1), 1-11.
[http://dx.doi.org/10.1111/j.1574-6968.2005.00001.x] [PMID: 16451172]
[7]
Engelbert, M.; Mylonakis, E.; Ausubel, F.M.; Calderwood, S.B.; Gilmore, M.S. Contribution of gelatinase, serine protease, and fsr to the pathogenesis of Enterococcus faecalis endophthalmitis. Infect. Immun., 2004, 72(6), 3628-3633.
[http://dx.doi.org/10.1128/IAI.72.6.3628-3633.2004] [PMID: 15155673]
[8]
Qin, X.; Singh, K.V.; Weinstock, G.M.; Murray, B.E. Effects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect. Immun., 2000, 68(5), 2579-2586.
[http://dx.doi.org/10.1128/IAI.68.5.2579-2586.2000] [PMID: 10768947]
[9]
Sifri, C.D.; Mylonakis, E.; Singh, K.V.; Qin, X.; Garsin, D.A.; Murray, B.E.; Ausubel, F.M.; Calderwood, S.B. Virulence effect of Enterococcus faecalis protease genes and the quorum-sensing locus fsr in Caenorhabditis elegans and mice. Infect. Immun., 2002, 70(10), 5647-5650.
[http://dx.doi.org/10.1128/IAI.70.10.5647-5650.2002] [PMID: 12228293]
[10]
Hancock, L.E.; Perego, M. The Enterococcus faecalis fsr two-component system controls biofilm development through production of gelatinase. J. Bacteriol., 2004, 186(17), 5629-5639.
[http://dx.doi.org/10.1128/JB.186.17.5629-5639.2004] [PMID: 15317767]
[11]
Nakayama, J.; Chen, S.; Oyama, N.; Nishiguchi, K.; Azab, E.A.; Tanaka, E.; Kariyama, R.; Sonomoto, K. Revised model for Enterococcus faecalis fsr quorum-sensing system: the small open reading frame fsrD encodes the gelatinase biosynthesis-activating pheromone propeptide corresponding to staphylococcal agrd. J. Bacteriol., 2006, 188(23), 8321-8326.
[http://dx.doi.org/10.1128/JB.00865-06] [PMID: 16980448]
[12]
Nakayama, J.; Cao, Y.; Horii, T.; Sakuda, S.; Akkermnas, A.D.L. Gelatinase biosynthesis-activating pheromone: A peptide lactone that mediates a quorum sensing in , 145-154.
[13]
Littlewood, S.; Tattersall, H.; Hughes, C.S.; Hussain, R.; Ma, P.; Harding, S.E.; Nakayama, J.; Phillips-Jones, M.K. The gelatinase biosynthesis-activating pheromone binds and stabilises the FsrB membrane protein in Enterococcus faecalis quorum sensing. FEBS Lett., 2020, 594(3), 553-563.
[http://dx.doi.org/10.1002/1873-3468.13634] [PMID: 31598959]
[14]
Ali, L.; Goraya, M.U.; Arafat, Y.; Ajmal, M.; Chen, J.L.; Yu, D. Molecular Mechanism of Quorum-Sensing in Enterococcus faecalis: Its Role in Virulence and Therapeutic Approaches. Int. J. Mol. Sci., 2017, 18(5), 1-19.
[http://dx.doi.org/10.3390/ijms18050960] [PMID: 28467378]
[15]
Moloney, M.G. Natural Products as a Source for Novel Antibiotics. Trends Pharmacol. Sci., 2016, 37(8), 689-701.
[http://dx.doi.org/10.1016/j.tips.2016.05.001] [PMID: 27267698]
[16]
Paul, R.K.; Dutta, D.; Chakraborty, D.; Nayak, A.; Dutta, P.K.; Nag, M. Antimicrobial agents from natural sources: An overview. Adv. Pharm. J., 2019, 4(2), 41-51.
[http://dx.doi.org/10.31024/apj.2019.4.2.1]
[17]
Paczkowski, J.E.; Mukherjee, S.; McCready, A.R.; Cong, J.P.; Aquino, C.J.; Kim, H.; Henke, B.R.; Smith, C.D.; Bassler, B.L. Aquino, C.J.; Kin, H.; Henke, B.R.; Bassler, B.L. Flavonoids suppress Pseudomonas aeruginosa virulence through allosteric inhibition of quorum-sensing Receptors. J. Biol. Chem., 2017, 292(10), 4064-4076.
[http://dx.doi.org/10.1074/jbc.M116.770552] [PMID: 28119451]
[18]
Deryabin, D.; Galadzhieva, A.; Kosyan, D.; Duskaev, G. Plant-derived inhibitors of AHL-mediated quorum sensing in bacteria: Modes of action. Int. J. Mol. Sci., 2019, 20(22), 1-22.
[http://dx.doi.org/10.3390/ijms20225588] [PMID: 31717364]
[19]
Nakayama, J.; Yokohata, R.; Sato, M.; Suzuki, T.; Matsufuji, T. Development of a Peptide Antagonist against fsr Quorum Sensing of Enterococcus faecalis. Am. Chem. Society, 2013, 8, 804-811.
[20]
Nakayama, J.; Tanaka, E.; Kariyama, R.; Nagata, K.; Nishiguchi, K.; Mitsuhata, R.; Uemura, Y.; Tanokura, M.; Kumon, H.; Sonomoto, K. Siamycin attenuates fsr quorum sensing mediated by a gelatinase biosynthesis-activating pheromone in Enterococcus faecalis. J. Bacteriol., 2007, 189(4), 1358-1365.
[http://dx.doi.org/10.1128/JB.00969-06] [PMID: 17071762]
[21]
Igarashi, Y.; Gohda, F.; Kadoshima, T.; Fukuda, T.; Hanafusa, T.; Shojima, A.; Nakayama, J.; Bills, G.F.; Peterson, S. Avellanin C, an inhibitor of quorum-sensing signaling in Staphylococcus aureus, from Hamigera ingelheimensis. J. Antibiot. (Tokyo), 2015, 68(11), 707-710.
[http://dx.doi.org/10.1038/ja.2015.50] [PMID: 25944536]
[22]
Desouky, S.E.; Shojima, A.; Singh, R.P.; Matsufuji, T.; Igarashi, Y.; Suzuki, T.; Yamagaki, T.; Okubo, K.; Ohtani, K.; Sonomoto, K.; Nakayama, J. Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria. FEMS Microbiol. Lett., 2015, 362(14), 1-9.
[http://dx.doi.org/10.1093/femsle/fnv109] [PMID: 26149266]
[23]
Igarashi, Y.; Yamamoto, K.; Fukuda, T.; Shojima, A.; Nakayama, J.; Carro, L.; Trujillo, M.E. Arthroamide, a Cyclic Depsipeptide with Quorum Sensing Inhibitory Activity from Arthrobacter sp. J. Nat. Prod., 2015, 78(11), 2827-2831.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00540] [PMID: 26575343]
[24]
Vandeputte, O.M.; Kiendrebeogo, M.; Rasamiravaka, T.; Stévigny, C.; Duez, P.; Rajaonson, S.; Diallo, B.; Mol, A.; Baucher, M.; El Jaziri, M. The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1. Microbiology, 2011, 157(Pt 7), 2120-2132.
[http://dx.doi.org/10.1099/mic.0.049338-0] [PMID: 21546585]
[25]
Eschenburg, S.; Priestman, M.; Schönbrunn, E. Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J. Biol. Chem., 2005, 280(5), 3757-3763.
[http://dx.doi.org/10.1074/jbc.M411325200] [PMID: 15531591]
[26]
Eschenburg, S.; Priestman, M.A.; Abdul-Latif, F.A.; Delachaume, C.; Fassy, F.; Schönbrunn, E. A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA). J. Biol. Chem., 2005, 280(14), 14070-14075.
[http://dx.doi.org/10.1074/jbc.M414412200] [PMID: 15701635]
[27]
Hartiani, T.; Sasmito, E. Sumardi; Ulfah, M. Preliminary Study on Immunomodulatory Effect of Sarang-Semut Tubers Myrmecodia tuberosa and Myrmecodia pendens. Online J. Biol. Sci., 2010, 10(3), 136-141.
[http://dx.doi.org/10.3844/ojbsci.2010.136.141]
[28]
Kurnia, D.; Sumiarsa, D.; Dharsono, H.D.A.; Satari, M.H. Bioactive compounds isolated from Indonesian epiphytic plant of Sarang Semut and their antibacterial activity against pathogenic oral bacteria. Nat. Prod. Commun., 2017, 12(8), 1201-1204.
[http://dx.doi.org/10.1177/1934578X1701200814]
[29]
Kurnia, D.; Apriyanti, E.; Soraya, C.; Satari, M.H. Antibacterial Flavonoids Against Oral Bacteria of Enterococcus Faecalis ATCC 29212 from Sarang Semut (Myrmecodia pendans) and Its Inhibitor Activity Against Enzyme MurA. Curr. Drug Discov. Technol., 2019, 16(3), 290-296.
[http://dx.doi.org/10.2174/1570163815666180828113920] [PMID: 30152286]
[30]
Cockerill, F.R.; Wiker, M.A.; Alder, J.; Dudley, M.N.; Eliopoulos, G.M.; Ferraro, M.J.; Hardy, D.J.; Hecht, D.W.; Hindler, J.A.; Patel, J.B.; Powell, M.; Swenson, J.M.; Thomson, R.B.; Traczewski, M.M.; Turnidge, J.D.; Weinstein, M.P.; Zimmer, B.L. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow AerobicallyApproved Standard — Ninth Edition, Clinical and Laboratory Standards Institute, Wayne, 2012, 32(2)
[31]
Cockerill, F.R.; Wiker, M.A.; Alder, J.; Dudley, M.N.; Eliopoulos, G.M.; Ferraro, M.J.; Hardy, D.J.; Hecht, D.W.; Hindler, J.A.; Patel, J.B.; Powell, M.; Swenson, J.M.; Thomson, R.B.; Traczewski, M.M.; Turnidge, J.D.; Weinstein, M.P.; Zimmer, B.L. Performance Standards for Antimicrobial Disk Susceptibility TestsApproved Standard — Eleventh Edition, Clinical and Laboratory Standards Institute, Wayne, 2012, 32, 1.
[32]
O’Boyle, N.M.; Banck, M.; James, C.A.; Morley, C.; Vandermeersch, T.; Hutchison, G.R. Open Babel: An open chemical toolbox. J. Cheminform., 2011, 3(33), 33.
[http://dx.doi.org/10.1186/1758-2946-3-33] [PMID: 21982300]
[33]
Biasini, M.; Bienert, S.; Waterhouse, A.; Arnold, K.; Studer, G.; Schmidt, T. kiefer, F. Cassarino, T.G.; Bertoni, M. Bordoli, L.; Schwede, T. SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res., 2014, 42(W1), 1-7.
[http://dx.doi.org/10.1093/nar/gku340]
[34]
Dallakyan, S.; Olson, A.J. Small-molecule library screening by docking with PyRx. Methods Mol. Biol., 2015, 1263, 243-250.
[http://dx.doi.org/10.1007/978-1-4939-2269-7_19] [PMID: 25618350]
[35]
Suprijono, M.M.; Widjanarko, S.B.; Sujuti, H.; Kurnia, D. Computational study of antioxidant activity and bioavailability of Papua red fruit (Pandanus conoideus Lam.) flavonoids through docking toward human serum albumin. Proceeding of the 3rd Scientific Meeting for Biomedical Sciences Malang, Indonesia, November 21-23;2018 , 1-9.
[http://dx.doi.org/10.1063/1.5109995]
[36]
Azam, S.S.; Abbasi, S.W. Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines. Theor. Biol. Med. Model., 2013, 10(63), 63.
[http://dx.doi.org/10.1186/1742-4682-10-63] [PMID: 24156411]
[37]
Rauf, M.A.; Zubair, S.; Azhar, A. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. Int. J. Sci.: Basic Appl., 2015, 4(2), 168-177.
[http://dx.doi.org/10.14419/ijbas.v4i2.4123]
[38]
Wang, C.M.; Hsu, Y.M.; Jhan, Y.L.; Tsai, S.J.; Lin, S.X.; Su, C.H.; Chou, C.H. Structure elucidation of procyanidins isolated from Rhododendron formosanum and their anti-oxidative and anti-bacterial activities. Molecules, 2015, 20(7), 12787-12803.
[http://dx.doi.org/10.3390/molecules200712787] [PMID: 26184152]
[39]
Aghamali, M.; Sedighi, M.; Zahedi Bialvaei, A.; Mohammadzadeh, N.; Abbasian, S.; Ghafouri, Z.; Kouhsari, E. Fosfomycin: mechanisms and the increasing prevalence of resistance. J. Med. Microbiol., 2019, 68(1), 11-25.
[http://dx.doi.org/10.1099/jmm.0.000874] [PMID: 30431421]
[40]
Nishiguchi, K.; Nagata, K.; Tanokura, M.; Sonomoto, K.; Nakayama, J. Structure-activity relationship of gelatinase biosynthesis-activating pheromone of Enterococcus faecalis. J. Bacteriol., 2009, 191(2), 641-650.
[http://dx.doi.org/10.1128/JB.01029-08] [PMID: 18996993]
[41]
Gök, Ş.M.; Türk Dağı, H.; Kara, F.; Arslan, U.; Fındık, D. Klinik Örneklerden İzole Edilen Enterococcus faecium ve Enterococcus faecalis İzolatlarının Antibiyotik Direnci ve Virülans Faktörlerinin Araştırılması. Mikrobiyol. Bul., 2020, 54(1), 26-39.
[PMID: 32050876]
[42]
Chen, D.; Oezguen, N.; Urvil, P.; Ferguson, C.; Dann, S.M.; Savidge, T.C. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Sci. Adv., 2016, 2(3)e1501240
[http://dx.doi.org/10.1126/sciadv.1501240] [PMID: 27051863]
[43]
Matsuda, H.; Wang, T.; Managi, H.; Yoshikawa, M. Structural requirements of flavonoids for inhibition of protein glycation and radical scavenging activities. Bioorg. Med. Chem., 2003, 11(24), 5317-5323.
[http://dx.doi.org/10.1016/j.bmc.2003.09.045] [PMID: 14642575]
[44]
Tibaut, T.; Drgan, V.; Novič, M. Application of SAR methods toward inhibition of bacterial peptidoglycan metabolizing enzymes. J. Chemometr., 2018, 32(4), 1-11.
[http://dx.doi.org/10.1002/cem.3007]
[45]
Ekins, S.; Mestres, J.; Testa, B. In silico pharmacology for drug discovery: applications to targets and beyond. Br. J. Pharmacol., 2007, 152(1), 21-37.
[http://dx.doi.org/10.1038/sj.bjp.0707306] [PMID: 17549046]

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