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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Exploring Nature’s Treasure to Inhibit β-Barrel Assembly Machinery of Antibiotic Resistant Bacteria: An In silico Approach

Author(s): Shalja Verma and Anand Kumar Pandey*

Volume 18, Issue 4, 2021

Published on: 24 December, 2020

Page: [325 - 337] Pages: 13

DOI: 10.2174/1570180818999201224121342

Price: $65

Abstract

Background: The development of antibiotic resistance in bacteria is a matter of global concern due to the exceptionally high morbidity and mortality rates. The outer membrane of most gram-negative bacteria acts as a highly efficient barrier and blocks the entry of the majority of antibiotics, making them ineffective. The Bam complex, β-barrel assembly machinery complex, contains five subunits (BamA, B, C, D, E), which plays a vital role in folding and inserting essential outer membrane proteins into the membrane, thus maintaining outer membrane integrity. BamA and BamD are essential subunits to fulfill this purpose. Therefore, targeting this complex to treat antibiotic resistance can be an incredibly effective approach. Natural bacterial pigments like violacein, phytochemicals like withanone, semasin, and several polyphenols have often been reported for their effective antibiotic, antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties.

Objective: Structural inhibition of the Bam complex by natural compounds can provide safe and effective treatment for antibiotic resistance by targeting outer membrane integrity.

Methods: In-silico ADMET and molecular docking analysis was performed with ten natural compounds, namely violacein, withanone, sesamin, resveratrol, naringenin, quercetin, epicatechin, gallic acid, ellagic acid, and galangin, to analyse their inhibitory potential against the Bam complex.

Results: Docking complexes of violacein gave high binding energies of -10.385 and -9.46 Kcal/mol at C and D subunits interface and at A subunits of the Bam complex, respectively.

Conclusion: Henceforth, violacein can be an effective antibiotic against to date reported resistant gram-negative bacteria by inhibiting the Bam complex of their outer membrane. Therefore the urgent need for exhaustive research in this concern is highly demanded.

Keywords: Antibiotic resistance, gram-negative bacteria, β-barrel assembly machinery (Bam) complex, outer membrane proteins, violacein.

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[1]
No time to wait: securing the future from drug-resistant infections. Report to the secretary-general of the united nations April 2019. Interagency coordination group on antimicrobial resistance. World Health Organisation, 2019, 1-28.https://www.who.int/docs/default-source/documents/no-time-to-wait-securing-the-future-from-drug-resistant-infections-en.pdf?sfvrsn=5b424d7_6
[2]
Lehman, K.M.; Grabowicz, M. Countering gram-negative antibiotic resistance: recent progress in disrupting the outer membrane with novel therapeutics. Antibiotics (Basel), 2019, 8(4), 1-18.
[http://dx.doi.org/10.3390/antibiotics8040163] [PMID: 31554212]
[3]
Aghapour, Z.; Gholizadeh, P.; Ganbarov, K.; Bialvaei, A.Z.; Mahmood, S.S.; Tanomand, A.; Yousefi, M.; Asgharzadeh, M.; Yousefi, B.; Kafil, H.S. Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Infect. Drug Resist., 2019, 12, 965-975.
[http://dx.doi.org/10.2147/IDR.S199844] [PMID: 31190901]
[4]
Delcour, A.H. Outer membrane permeability and antibiotic resistance. Biochim. Biophys. Acta, 2009, 1794(5), 808-816.
[http://dx.doi.org/10.1016/j.bbapap.2008.11.005] [PMID: 19100346]
[5]
Silhavy, T.J.; Kahne, D.; Walker, S. The bacterial cell envelope. Cold Spring Harb. Perspect. Biol., 2010, 2(5), a000414.
[http://dx.doi.org/10.1101/cshperspect.a000414] [PMID: 20452953]
[6]
Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev., 2003, 67(4), 593-656.
[http://dx.doi.org/10.1128/MMBR.67.4.593-656.2003] [PMID: 14665678]
[7]
Fernández, L.; Hancock, R.E. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin. Microbiol. Rev., 2012, 25(4), 661-681.
[http://dx.doi.org/10.1128/CMR.00043-12] [PMID: 23034325]
[8]
Alexander, M.K.; Miu, A.; Oh, A.; Reichelt, M.; Ho, H.; Chalouni, C.; Labadie, S.; Wang, L.; Liang, J.; Nickerson, N.N.; Hu, H.; Yu, L.; Du, M.; Yan, D.; Park, S.; Kim, J.; Xu, M.; Sellers, B.D.; Purkey, H.E.; Skelton, N.J.; Koehler, M.F.T.; Payandeh, J.; Verma, V.; Xu, Y.; Koth, C.M.; Nishiyama, M. Disrupting gram-negative bacterial outer membrane biosynthesis through inhibition of the lipopolysaccharide transporter MsbA. Antimicrob. Agents Chemother., 2018, 62(11), 1-15.
[http://dx.doi.org/10.1128/AAC.01142-18] [PMID: 30104274]
[9]
Robinson, J.A. folded synthetic peptides and other molecules targeting outer membrane protein complexes in gram-negative bacteria. Front Chem., 2019, 7(45), 45.
[http://dx.doi.org/10.3389/fchem.2019.00045] [PMID: 30788339]
[10]
Wu, R.; Stephenson, R.; Gichaba, A.; Noinaj, N. The big BAM theory: An open and closed case? Biochim. Biophys. Acta Biomembr., 2020, 1862(1), 183062.
[http://dx.doi.org/10.1016/j.bbamem.2019.183062] [PMID: 31520605]
[11]
Malinverni, J.C.; Silhavy, T.J. Assembly of outer membrane β-barrel proteins: the Bam complex. Ecosal Plus, 2011, 4(2), 1-33.
[http://dx.doi.org/10.1128/ecosalplus.4.3.8] [PMID: 26442509]
[12]
Kim, K.H.; Aulakh, S.; Paetzel, M. The bacterial outer membrane β-barrel assembly machinery. Protein Sci., 2012, 21(6), 751-768.
[http://dx.doi.org/10.1002/pro.2069] [PMID: 22549918]
[13]
Han, L.; Zheng, J.; Wang, Y.; Yang, X.; Liu, Y.; Sun, C.; Cao, B.; Zhou, H.; Ni, D.; Lou, J.; Zhao, Y.; Huang, Y. Structure of the BAM complex and its implications for biogenesis of outer-membrane proteins. Nat. Struct. Mol. Biol., 2016, 23(3), 192-196.
[http://dx.doi.org/10.1038/nsmb.3181] [PMID: 26900875]
[14]
Fleming, P.J.; Patel, D.S.; Wu, E.L.; Qi, Y.; Yeom, M.S.; Sousa, M.C.; Fleming, K.G. Im, W. Im, W. BamA POTRA domain interacts with a native lipid membrane surface. Biophys. J., 2016, 110(12), 2698-2709.
[http://dx.doi.org/10.1016/j.bpj.2016.05.010] [PMID: 27332128]
[15]
Ricci, D.P.; Silhavy, T.J. Outer membrane protein insertion by the β-barrel assembly machine. Ecosal Plus, 2019, 8(2), 1-14.
[PMID: 30869065]
[16]
Knowles, T.J.; Scott-Tucker, A.; Overduin, M.; Henderson, I.R. Membrane protein architects: the role of the BAM complex in outer membrane protein assembly. Nat. Rev. Microbiol., 2009, 7(3), 206-214.
[http://dx.doi.org/10.1038/nrmicro2069] [PMID: 19182809]
[17]
Storek, K.M.; Auerbach, M.R.; Shi, H.; Garcia, N.K.; Sun, D.; Nickerson, N.N.; Vij, R.; Lin, Z.; Chiang, N.; Schneider, K.; Wecksler, A.T.; Skippington, E.; Nakamura, G.; Seshasayee, D.; Koerber, J.T.; Payandeh, J.; Smith, P.A.; Rutherford, S.T. Monoclonal antibody targeting the β-barrel assembly machine of Escherichia coli is bactericidal. Proc. Natl. Acad. Sci. USA, 2018, 115(14), 3692-3697.
[http://dx.doi.org/10.1073/pnas.1800043115] [PMID: 29555747]
[18]
Fair, R.J.; Tor, Y. Antibiotics and bacterial resistance in the 21st century. Perspect. Medicin. Chem., 2014, 6, 25-64.
[http://dx.doi.org/10.4137/PMC.S14459] [PMID: 25232278]
[19]
Hart, E.M.; Mitchell, A.M.; Konovalova, A.; Grabowicz, M.; Sheng, J.; Han, X.; Rodriguez-Rivera, F.P.; Schwaid, A.G.; Malinverni, J.C.; Balibar, C.J.; Bodea, S.; Si, Q.; Wang, H.; Homsher, M.F.; Painter, R.E.; Ogawa, A.K.; Sutterlin, H.; Roemer, T.; Black, T.A.; Rothman, D.M.; Walker, S.S.; Silhavy, T.J. A small molecule inhibitor of BamA impervious to efflux and the outer membrane permeability barrier. Proc. Natl. Acad. Sci. USA, 2019, 116(43), 21748-21757.
[20]
Puertollano, M.A.; Puertollano, E.; de Cienfuegos, G.Á.; de Pablo, M.A. Dietary antioxidants: immunity and host defense. Curr. Top. Med. Chem., 2011, 11(14), 1752-1766.
[http://dx.doi.org/10.2174/156802611796235107] [PMID: 21506934]
[21]
Choi, S.Y.; Lim, S.; Cho, G.; Kwon, J.; Mun, W.; Im, H.; Mitchell, R.J. Chromobacterium violaceum delivers violacein, a hydrophobic antibiotic, to other microbes in membrane vesicles. Environ. Microbiol., 2020, 22(2), 705-713.
[http://dx.doi.org/10.1111/1462-2920.14888] [PMID: 31814287]
[22]
Priyandoko, D.; Ishii, T.; Kaul, S.C.; Wadhwa, R. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite. PLoS One, 2011, 6(5), e19552.
[http://dx.doi.org/10.1371/journal.pone.0019552] [PMID: 21573189]
[23]
Dutta, R.; Khalil, R.; Green, R.; Mohapatra, S.S.; Mohapatra, S. Withania somnifera (ashwagandha) and withaferin A: potential in integrative oncology. Int. J. Mol. Sci., 2019, 20(21), 1-19.
[http://dx.doi.org/10.3390/ijms20215310] [PMID: 31731424]
[24]
Xie, Y.; Yang, W.; Tang, F.; Chen, X.; Ren, L. Antibacterial activities of flavonoids: structure-activity relationship and mechanism. Curr. Med. Chem., 2015, 22(1), 132-149.
[http://dx.doi.org/10.2174/0929867321666140916113443] [PMID: 25245513]
[25]
Pathak, N.; Bhaduri, A.; Rai, A.K. Sesame: Bioactive Compounds and Health Benefits.Bioactive Molecules in Food. Reference Series in Phytochemistry; Mérillon, J.M.; Ramawat, K., Eds; Springer Cham, 2018, pp. 1-20.
[26]
Papuc, C.; Goran, G.V.; Predescu, C.N.; Nicorescu, V.; Stefan, G. Plant polyphenols as antioxidant and antibacterial agents for shelf‐life extension of meat and meat products: classification, structures, sources, and action mechanisms. Compr. Rev. Food Sci. Food Saf., 2017, 16, 1243-1268.
[http://dx.doi.org/10.1111/1541-4337.12298]
[27]
Mattio, L.M.; Dallavalle, S.; Musso, L.; Filardi, R.; Franzetti, L.; Pellegrino, L.; D’Incecco, P.; Mora, D.; Pinto, A.; Arioli, S. Antimicrobial activity of resveratrol-derived monomers and dimers against foodborne pathogens. Sci. Rep., 2019, 9(1), 19525.
[http://dx.doi.org/10.1038/s41598-019-55975-1] [PMID: 31862939]
[28]
Agus, S.; Achmadi, S.S.; Mubarik, N.R. Antibacterial activity of naringenin-rich fraction of pigeon pea leaves toward Salmonella thypi. Asian Pac. J. Trop. Biomed., 2017, 7(8), 725-728.
[http://dx.doi.org/10.1016/j.apjtb.2017.07.019]
[29]
Xing, Z.C.; Meng, W.; Yuan, J.; Moon, S.; Jeong, Y.; Kang, I.K. In vitro assessment of antibacterial activity and cytocompatibility of quercetin-containing PLGA nanofibrous scaffolds for tissue engineering. J. Nanomater., 2012, 2012(202608), 1-7.
[http://dx.doi.org/10.1155/2012/202608]
[30]
Adamczak, A.; Ożarowski, M.; Karpiński, T.M. Antibacterial activity of some flavonoids and organic acids widely distributed in plants. J. Clin. Med., 2019, 9(1), 1-17.
[http://dx.doi.org/10.3390/jcm9010109] [PMID: 31906141]
[31]
Escandón, R.A.; del Campo, M.; López-Solis, R. Antibacterial effect of kaempferol and (−)-epicatechin on Helicobacter pylori. Eur. Food Res. Technol., 2016, 242, 1495-1502.
[http://dx.doi.org/10.1007/s00217-016-2650-z]
[32]
Borges, A.; Ferreira, C.; Saavedra, M.J.; Simões, M. Antibacterial activity and mode of action of ferulic and gallic acids against pathogenic bacteria. Microb. Drug Resist., 2013, 19(4), 256-265.
[http://dx.doi.org/10.1089/mdr.2012.0244] [PMID: 23480526]
[33]
De, R.; Sarkar, A.; Ghosh, P.; Ganguly, M.; Karmakar, B.C.; Saha, D.R.; Halder, A.; Chowdhury, A.; Mukhopadhyay, A.K. Antimicrobial activity of ellagic acid against Helicobacter pylori isolates from India and during infections in mice. J. Antimicrob. Chemother., 2018, 73(6), 1595-1603.
[http://dx.doi.org/10.1093/jac/dky079] [PMID: 29566160]
[34]
Pepeljnjak, S.; Kosalec, I. Galangin expresses bactericidal activity against multiple-resistant bacteria: MRSA, Enterococcus spp. and Pseudomonas aeruginosa. FEMS Microbiol. Lett., 2004, 240(1), 111-116.
[http://dx.doi.org/10.1016/j.femsle.2004.09.018] [PMID: 15500987]
[35]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7(42717), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[36]
Banerjee, P.; Eckert, O.A.; Schrey, A.K.; Preissner, R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res., 2018.
[http://dx.doi.org/10.1093/nar/gky318]
[37]
Ventola, C.L. The antibiotic resistance crisis: part 1: causes and threats. P&T, 2015, 40(4), 277-283.
[PMID: 25859123]
[38]
Zgurskaya, H.I.; Löpez, C.A.; Gnanakaran, S. Permeability barrier of gram-negative cell envelopes and approaches to bypass it. ACS Infect. Dis., 2015, 1(11), 512-522.
[http://dx.doi.org/10.1021/acsinfecdis.5b00097] [PMID: 26925460]
[39]
Annunziato, G. Strategies to overcome antimicrobial resistance (AMR) making use of non-essential target inhibitors: a review. Int. J. Mol. Sci., 2019, 20(23), 1-25.
[http://dx.doi.org/10.3390/ijms20235844] [PMID: 31766441]
[40]
Rollauer, S.E.; Sooreshjani, M.A.; Noinaj, N.; Buchanan, S.K. Outer membrane protein biogenesis in Gram-negative bacteria. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2015, 370(1679), 1-10.
[http://dx.doi.org/10.1098/rstb.2015.0023] [PMID: 26370935]
[41]
Leyton, D.L.; Belousoff, M.J.; Lithgow, T. The β-barrel assembly machinery complex. Methods Mol. Biol., 2015, 1329, 1-16.
[http://dx.doi.org/10.1007/978-1-4939-2871-2_1] [PMID: 26427672]
[42]
Plummer, A.M.; Fleming, K.G. From chaperones to the membrane with a BAM! Trends Biochem. Sci., 2016, 41(10), 872-882.
[http://dx.doi.org/10.1016/j.tibs.2016.06.005] [PMID: 27450425]
[43]
Hagan, C.L.; Wzorek, J.S.; Kahne, D. Inhibition of the β-barrel assembly machine by a peptide that binds BamD. Proc. Natl. Acad. Sci. USA, 2015, 112(7), 2011-2016.
[http://dx.doi.org/10.1073/pnas.1415955112] [PMID: 25646443]
[44]
Jores, T.; Klinger, A.; Groß, L.E.; Kawano, S.; Flinner, N.; Duchardt-Ferner, E.; Wöhnert, J.; Kalbacher, H.; Endo, T.; Schleiff, E.; Rapaport, D. Characterization of the targeting signal in mitochondrial β-barrel proteins. Nat. Commun., 2016, 7(12036), 12036.
[http://dx.doi.org/10.1038/ncomms12036] [PMID: 27345737]
[45]
Urfer, M.; Bogdanovic, J.; Lo Monte, F.; Moehle, K.; Zerbe, K.; Omasits, U.; Ahrens, C.H.; Pessi, G.; Eberl, L.; Robinson, J.A. A peptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in Escherichia coli. J. Biol. Chem., 2016, 291(4), 1921-1932.
[http://dx.doi.org/10.1074/jbc.M115.691725] [PMID: 26627837]
[46]
Din, F.U.; Aman, W.; Ullah, I.; Qureshi, O.S.; Mustapha, O.; Shafique, S.; Zeb, A. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int. J. Nanomedicine, 2017, 12, 7291-7309.
[http://dx.doi.org/10.2147/IJN.S146315] [PMID: 29042776]
[47]
Cauz, A.C.G.; Carretero, G.P.B.; Saraiva, G.K.V.; Park, P.; Mortara, L.; Cuccovia, I.M.; Brocchi, M.; Gueiros-Filho, F.J. Violacein targets the cytoplasmic membrane of bacteria. ACS Infect. Dis., 2019, 5(4), 539-549.
[http://dx.doi.org/10.1021/acsinfecdis.8b00245] [PMID: 30693760]

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