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Current Chemical Biology

Editor-in-Chief

ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

General Research Article

Ebselen’s Potential to Inhibit Planktonic and Biofilm Growth of Neisseria mucosa

Author(s): Shaukat A. Shaikh, Indira K. Priyadarsini* and Sirisha L. Vavilala*

Volume 16, Issue 1, 2022

Published on: 10 June, 2022

Page: [61 - 69] Pages: 9

DOI: 10.2174/2212796816666220330090107

Abstract

Background: Antibiotic resistance of various bacterial communities remains a global burden in the healthcare industry. Biofilm formation is one of the resistance mechanisms acquired by bacterial communities in order to reverse the action of antibiotics. There is an urgent need for the discovery of novel antimicrobials and novel approaches to tackle this problem. However, it is very expensive and challenging to develop new antibiotics. Drug repurposing is an efficient strategy which reduces time and cost associated with drug discovery.

Objective: In the current study, anti-microbial and antibiofilm potential of an organoselenium clinical molecule Ebselen against Neisseria mucosa has been elucidated.

Methods: Ebselen Antibacterial studies include Minimum Inhibitory Concentration (MIC), growthkill, Colony Forming Unit (CFU) assays and intracellular Reactive Oxygen Species (ROS) accumulation studies. Antibiofilm studies included inhibition, eradication and cell surface hydrophobicity assays, quantification of Extracellular Polymeric Substance (EPS) and eDNA and for anti-quorum sensing activity, protease and urease enzyme activities were elucidated.

Results: Ebselen showed efficient bactericidal activity as indicated by its low MIC values, bacterial growth inhibition over time and its ability to prevent clonal propagation in this bacterium. Increased accumulation of ROS in Ebselen treated cells indicates radical mediated induction of bacterial death. Interestingly, Ebselen inhibited and distorted matured biofilms by degrading the eDNA component of the EPS layer. Ebselen also attenuated quorum-sensing pathway as indicated by decreased urease and protease enzyme activities.

Conclusion: Taken together, these results paved the way to repurpose Ebselen as a potential drug target to curb Neisseria mucosa infections.

Keywords: Neisseria mucosa, ebselen, biofilm inhibition, quorum sensing, drug repurposing, biofilm growth.

Graphical Abstract
[1]
Prestinaci, F.; Pezzotti, P.; Pantosti, A. Antimicrobial resistance: A global multifaceted phenomenon. Pathog. Glob. Health, 2015, 109(7), 309-318.
[http://dx.doi.org/10.1179/2047773215Y.0000000030] [PMID: 26343252]
[2]
Yang, X.; Guo, R.; Xie, B.; Lai, Q.; Xu, J.; Hu, N.; Wan, L.; Dai, M.; Zhang, B. Drug resistance of pathogens causing nosocomial infection in orthopedics from 2012 to 2017: A 6-year retrospective study. J. Orthop. Surg. Res., 2021, 16(1), 100.
[http://dx.doi.org/10.1186/s13018-021-02234-7] [PMID: 33522930]
[3]
Munita, J.M.; Arias, C.A. Mechanisms of antibiotic resistance. Microbiol. Spectr., 2016, 4(2)
[http://dx.doi.org/10.1128/microbiolspec.VMBF-0016-2015] [PMID: 27227291]
[4]
van Hoek, A.H.; Mevius, D.; Guerra, B.; Mullany, P.; Roberts, A.P.; Aarts, H.J. Acquired antibiotic resistance genes: An overview. Front. Microbiol., 2011, 2, 203.
[http://dx.doi.org/10.3389/fmicb.2011.00203] [PMID: 22046172]
[5]
Roy, R.; Tiwari, M.; Donelli, G.; Tiwari, V. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence, 2018, 9(1), 522-554.
[http://dx.doi.org/10.1080/21505594.2017.1313372] [PMID: 28362216]
[6]
Annunziato, G. Strategies to overcome antimicrobial resistance (AMR) making use of non-essential target inhibitors: A review. Int. J. Mol. Sci., 2019, 20(23), 5844.
[http://dx.doi.org/10.3390/ijms20235844] [PMID: 31766441]
[7]
Reygaert, W.C. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol., 2018, 4(3), 482-501.
[http://dx.doi.org/10.3934/microbiol.2018.3.482] [PMID: 31294229]
[8]
Lécuyer, F.; Bourassa, J.S.; Gélinas, M.; Charron-Lamoureux, V.; Burrus, V.; Beauregard, P.B. Biofilm formation drives transfer of the conjugative element ICEBs1 in Bacillus subtilis. MSphere, 2018, 3(5), e00473-e18.
[http://dx.doi.org/10.1128/mSphere.00473-18] [PMID: 30258041]
[9]
Serra, D.O.; Hengge, R. Stress responses shape biofilm architecture. Environ. Microbiol., 2014, 16, 1455-1471.
[http://dx.doi.org/10.1111/1462-2920.12483] [PMID: 24725389]
[10]
Kamble, S.C.; Patil, S.N. Technological developments in quorum sensing and its inhibition for medical applications. Biotechnological Applications of Quorum Sensing Inhibitors; Kalia, V., Ed.; Springer: Singapore, 2018.
[http://dx.doi.org/10.1007/978-981-10-9026-4_14]
[11]
Sankar, G.P.; Ravishankar, R.V. Alternative strategies to regulate quorum sensing and biofilm formation of pathogenic Pseudomonas by quorum sensing inhibitors of diverse origins. Biotechnological Applications of Quorum Sensing Inhibitors. Springer, 2018, 10, 978-981.
[http://dx.doi.org/10.1007/978-981-10-9026-4_3]
[12]
Subramani, R.; Jayaprakashvel, M. Bacterial quorum sensing: Biofilm formation, survival behaviour and antibiotic resistance. Implication of Quorum Sensing and Biofilm Formation in Medicine, Agriculture and Food Industry; Bramhachari, P., Ed.; Springer: Singapore, 2019.
[http://dx.doi.org/10.1007/978-981-32-9409-7_3]
[13]
Ventola, C.L. The antibiotic resistance crisis: Part 2: Management strategies and new agents. PT, 2015, 40(5), 344-352.
[PMID: 25987823]
[14]
Schewe, T. Molecular actions of ebselen--an antiinflammatory antioxidant. Gen. Pharmacol., 1995, 26(6), 1153-1169.
[http://dx.doi.org/10.1016/0306-3623(95)00003-J] [PMID: 7590103]
[15]
Azad, G.K.; Tomar, R.S. Ebselen, a promising antioxidant drug: Mechanisms of action and targets of biological pathways. Mol. Biol. Rep., 2014, 41(8), 4865-4879.
[http://dx.doi.org/10.1007/s11033-014-3417-x] [PMID: 24867080]
[16]
Lu, Q.; Cai, Y.; Xiang, C.; Wu, T.; Zhao, Y.; Wang, J.; Wang, H.; Zou, L. Ebselen, a multi-target compound: Its effects on biological processes and diseases. Expert Rev. Mol. Med., 2021, 23, E12.
[http://dx.doi.org/10.1017/erm.2021.14]
[17]
Santi, C.; Scimmi, C.; Sancineto, L. Ebselen and Analogues: Pharmacological properties and synthetic strategies for their preparation. Molecules, 2021, 26(14), 4230.
[http://dx.doi.org/10.3390/molecules26144230] [PMID: 34299505]
[18]
Felix, L.; Mylonakis, E.; Fuchs, B.B. Thioredoxin reductase is a valid target for antimicrobial therapeutic development against gram-positive bacteria. Front. Microbiol., 2021, 12, 663481.
[http://dx.doi.org/10.3389/fmicb.2021.663481] [PMID: 33936021]
[19]
Dong, C.; Zhou, J.; Wang, P.; Li, T.; Zhao, Y.; Ren, X.; Lu, J.; Wang, J.; Holmgren, A.; Zou, L. Topical therapeutic efficacy of ebselen against multidrug-resistant Staphylococcus aureus LT-1 targeting thioredoxin reductase. Front. Microbiol., 2020, 10, 3016.
[http://dx.doi.org/10.3389/fmicb.2019.03016] [PMID: 32010088]
[20]
Lu, J.; Vlamis-Gardikas, A.; Kandasamy, K.; Zhao, R.; Gustafsson, T.N.; Engstrand, L.; Hoffner, S.; Engman, L.; Holmgren, A. Inhibition of bacterial thioredoxin reductase: An antibiotic mechanism targeting bacteria lacking glutathione. FASEB J., 2013, 27(4), 1394-1403.
[http://dx.doi.org/10.1096/fj.12-223305] [PMID: 23248236]
[21]
Thangamani, S.; Younis, W.; Seleem, M.N. Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections. Sci. Rep., 2015, 5(1), 11596.
[http://dx.doi.org/10.1038/srep11596] [PMID: 26111644]
[22]
Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved standard, 6th ed; CLSI: Wayne, Pa., USA, 2003.
[23]
Mogana, R.; Adhikari, A.; Tzar, M.N.; Ramliza, R.; Wiart, C. Antibacterial activities of the extracts, fractions and isolated compounds from Canarium patentinervium Miq. against bacterial clinical isolates. BMC Complement Med Ther, 2020, 20(1), 55.
[http://dx.doi.org/10.1186/s12906-020-2837-5] [PMID: 32059725]
[24]
Casciato, D.A.; Stewart, P.R.; Rosenblatt, J.E. Growth curves of anaerobic bacteria in solid media. Appl. Microbiol., 1975, 29(5), 610-614.
[http://dx.doi.org/10.1128/am.29.5.610-614.1975] [PMID: 167660]
[25]
Velema, W.A.; van der Berg, J.P.; Hansen, M.J.; Szymanski, W.; Driessen, A.J.; Feringa, B.L. Optical control of antibacterial activity. Nat. Chem., 2013, 5(11), 924-928.
[http://dx.doi.org/10.1038/nchem.1750] [PMID: 24153369]
[26]
Pinto, N.C.C.; Silva, J.B.; Menegati, L.M.; Guedes, M.C.M.R.; Marques, L.B.; Silva, T.P.D.; Melo, R.C.N.; Souza-Fagundes, E.M.; Salvador, M.J.; Scio, E.; Fabri, R.L. Cytotoxicity and bacterial membrane destabilization induced by Annona squamosa L. extracts. An. Acad. Bras. Cienc., 2017, 89(3)(Suppl.), 2053-2073.
[http://dx.doi.org/10.1590/0001-3765201720150702] [PMID: 28813096]
[27]
Foucaud, L.; Wilson, M.R.; Brown, D.M.; Stone, V. Measurement of reactive species production by nanoparticles prepared in biologically relevant media. Toxicol. Lett., 2007, 174(1-3), 1-9.
[http://dx.doi.org/10.1016/j.toxlet.2007.08.001] [PMID: 17888595]
[28]
Wang, H.; Joseph, J.A. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic. Biol. Med., 1999, 27(5-6), 612-616.
[http://dx.doi.org/10.1016/S0891-5849(99)00107-0] [PMID: 10490282]
[29]
Bazargani, M.M.; Jens, R. Anti-biofilm activity of essential oils and plant extracts against Staphylococcus aureus and E. coli biofilms. Food Control, 2015, 61, 156-164.
[http://dx.doi.org/10.1016/j.foodcont.2015.09.036]
[30]
Vishwakarma, J. v L, S. Unraveling the anti-biofilm potential of green algal sulfated polysaccharides against Salmonella enterica and Vibrio harveyi. Appl. Microbiol. Biotechnol., 2020, 104(14), 6299-6314.
[http://dx.doi.org/10.1007/s00253-020-10653-5] [PMID: 32451587]
[31]
Patel, B.; Mishra, S.; Priyadarsini, I.K.; Vavilala, S.L. Elucidating the anti-biofilm and anti-quorum sensing potential of selenocystine against respiratory tract infections causing bacteria: In vitro and in silico studies. Biol. Chem., 2021, 402(7), 769-783.
[http://dx.doi.org/10.1515/hsz-2020-0375] [PMID: 33735944]
[32]
Kauffmann, F.; Møller, V. On amino acid decarboxylases of Salmonella types and on the KCN test. Acta Pathol. Microbiol. Scand., 1955, 36(2), 173-178.
[http://dx.doi.org/10.1111/j.1699-0463.1955.tb04584.x] [PMID: 14375938]
[33]
Dalal, R. Screening and isolation of protease producing bacteria from soil collected from different areas of Burhanpur region (MP) India. Int. J. Curr. Microbiol. Appl. Sci., 2015, 4, 597-606.
[34]
Jamal, M.; Ahmad, W.; Andleeb, S.; Jalil, F.; Imran, M.; Nawaz, M.A.; Hussain, T.; Ali, M.; Rafiq, M.; Kamil, M.A. Bacterial biofilm and associated infections. J. Chin. Med. Assoc., 2018, 81(1), 7-11.
[http://dx.doi.org/10.1016/j.jcma.2017.07.012] [PMID: 29042186]
[35]
Bjarnsholt, T. The role of bacterial biofilms in chronic infections. APMIS Suppl, 2013, 136, 1-51.
[http://dx.doi.org/10.1111/apm.12099]
[36]
Nozawa, R; Yokota, T; Fujimoto, T. Susceptibility of methicillinresistant Staphylococcus aureus to the selenium-containing compound 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (PZ51). Antimicrob agen chemothe, 1989, 33, 1388-1390.
[37]
Sakurai, T.; Kanayama, M.; Shibata, T.; Itoh, K.; Kobayashi, A.; Yamamoto, M.; Uchida, K. Ebselen, a seleno-organic antioxidant, as an electrophile. Chem. Res. Toxicol., 2006, 19(9), 1196-1204.
[http://dx.doi.org/10.1021/tx0601105] [PMID: 16978024]
[38]
Handa, Y.; Kaneko, M.; Takeuchi, H.; Tsuchida, A.; Kobayashi, H.; Kubota, T. Effect of an antioxidant, ebselen, on development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates. Surg. Neurol., 2000, 53(4), 323-329.
[http://dx.doi.org/10.1016/S0090-3019(00)00168-3] [PMID: 10825515]
[39]
Kobayashi, T.; Ohta, Y.; Yoshino, J. Preventive effect of ebselen on acute gastric mucosal lesion development in rats treated with compound 48/80. Eur. J. Pharmacol., 2001, 414(2-3), 271-279.
[http://dx.doi.org/10.1016/S0014-2999(01)00815-9] [PMID: 11239928]
[40]
Parnham, M.J.; Sies, H. The early research and development of ebselen. Biochem. Pharmacol., 2013, 86(9), 1248-1253.
[http://dx.doi.org/10.1016/j.bcp.2013.08.028] [PMID: 24012716]
[41]
Singh, N.; Halliday, A.C.; Thomas, J.M.; Kuznetsova, O.V.; Baldwin, R.; Woon, E.C.; Aley, P.K.; Antoniadou, I.; Sharp, T.; Vasudevan, S.R.; Churchill, G.C. A safe lithium mimetic for bipolar disorder. Nat. Commun., 2013, 4(1), 1332.
[http://dx.doi.org/10.1038/ncomms2320] [PMID: 23299882]
[42]
Gustafsson, T.N.; Osman, H.; Werngren, J.; Hoffner, S.; Engman, L.; Holmgren, A. Ebselen and analogs as inhibitors of Bacillus anthracis thioredoxin reductase and bactericidal antibacterials targeting Bacillus species, Staphylococcus aureus and Mycobacterium tuberculosis. Biochim. Biophys. Acta, 2016, 1860(6), 1265-1271.
[http://dx.doi.org/10.1016/j.bbagen.2016.03.013] [PMID: 26971857]
[43]
Sharma, D.; Misba, L.; Khan, A.U. Antibiotics versus biofilm: An emerging battleground in microbial communities. Antimicrob. Resist. Infect. Control, 2019, 8(1), 76.
[http://dx.doi.org/10.1186/s13756-019-0533-3] [PMID: 31131107]
[44]
AbdelKhalek, A.; Abutaleb, N.S.; Mohammad, H.; Seleem, M.N. Repurposing ebselen for decolonization of vancomycin-resistant enterococci (VRE). PLoS One, 2018, 13, 6.
[45]
Molina-Manso, D.; del Prado, G.; Ortiz-Pérez, A.; Manrubia-Cobo, M.; Gómez-Barrena, E.; Cordero-Ampuero, J.; Esteban, J. In vitro susceptibility to antibiotics of staphylococci in biofilms isolated from orthopaedic infections. Int. J. Antimicrob. Agents, 2013, 41(6), 521-523.
[http://dx.doi.org/10.1016/j.ijantimicag.2013.02.018] [PMID: 23611308]
[46]
Nazzaro, F.; Fratianni, F.; d’Acierno, A.; De Feo, V.; Ayala-Zavala, F.J.; Gomes-Cruz, A.; Coppola, R. Effect of polyphenols on microbial cell-cell communications,” in Quorum Sensing: Molecular mechanism and biotechnological application. Advances in Food and Nutrition Research; Gomes da Cruz, A.; Prudencio, E.S.; Esmerino, E.A.; Cristina da Silva, M., Eds.; Academic Press: Cambridge, MA, 2019, pp. 195-223.
[47]
Steindler, L.; Venturi, V. Detection of quorum-sensing N-acyl homoserine lactone signal molecules by bacterial biosensors. FEMS Microbiol. Lett., 2007, 266(1), 1-9.
[http://dx.doi.org/10.1111/j.1574-6968.2006.00501.x] [PMID: 17233715]
[48]
Kumari, A.; Pasini, P.; Deo, S.K.; Flomenhoft, D.; Shashidhar, H.; Daunert, S. Biosensing systems for the detection of bacterial quorum signaling molecules. Anal. Chem., 2006, 78(22), 7603-7609.
[http://dx.doi.org/10.1021/ac061421n] [PMID: 17105149]
[49]
Duerkop, B.A.; Ulrich, R.L.; Greenberg, E.P. Octanoyl-homoserine lactone is the cognate signal for Burkholderia mallei BmaR1-BmaI1 quorum sensing. J. Bacteriol., 2007, 189(14), 5034-5040.
[http://dx.doi.org/10.1128/JB.00317-07] [PMID: 17496085]
[50]
Withers, H.; Swift, S.; Williams, P. Quorum sensing as an integral component of gene regulatory networks in Gram-negative bacteria. Curr. Opin. Microbiol., 2001, 4(2), 186-193.
[http://dx.doi.org/10.1016/S1369-5274(00)00187-9] [PMID: 11282475]
[51]
Jiang, Q.; Chen, J.; Yang, C.; Yin, Y.; Yao, K. Quorum sensing: A prospective therapeutic target for bacterial diseases. BioMed Res. Int., 2019, 2019, 2015978.
[http://dx.doi.org/10.1155/2019/2015978] [PMID: 31080810]
[52]
Whiteley, M.; Diggle, S.P.; Greenberg, E.P. Bacterial quorum sensing: The progress and promise of an emerging research area. Nature, 2017, 551, 313-320.
[http://dx.doi.org/10.1038/nature24624] [PMID: 29144467]
[53]
Abisado, R.G.; Benomar, S.; Klaus, J.R.; Dandekar, A.A.; Chandler, J.R. Bacterial quorum sensing and microbial community interactions. MBio, 2018, 9(3), e02331-e02417.
[http://dx.doi.org/10.1128/mBio.02331-17] [PMID: 29789364]
[54]
Grandclément, C.; Tannières, M.; Moréra, S.; Dessaux, Y.; Faure, D. Quorum quenching: Role in nature and applied developments. FEMS Microbiol. Rev., 2016, 40(1), 86-116.
[http://dx.doi.org/10.1093/femsre/fuv038] [PMID: 26432822]
[55]
Gajdács, M.; Urbán, E. Epidemiological trends and resistance associated with Stenotrophomonas maltophilia Bacteremia: A 10-Year retrospective cohort study in a tertiary-care hospital in hungary. Diseases, 2019, 7(2), 41.
[http://dx.doi.org/10.3390/diseases7020041] [PMID: 31159258]
[56]
Turovskiy, Y.; Kashtanov, D.; Paskhover, B.; Chikindas, M.L. Quorum sensing: Fact, fiction, and everything in between. Adv. Appl. Microbiol., 2007, 62, 191-234.
[http://dx.doi.org/10.1016/S0065-2164(07)62007-3] [PMID: 17869606]
[57]
Rutherford, S.T. Bassler, BL Bacterial quorum sensing: Its role in virulence and possibilities for its control. Cold Spring Harb. Perspect. Med., 2012, 2(11), a012427.
[http://dx.doi.org/10.1101/cshperspect.a012427]
[58]
Yong, Y.C.; Zhong, J.J. Impacts of quorum sensing on microbial metabolism and human health.Future Trends in Biotechnology; Zhong, J-J., Ed.; Springer: Berlin/Heidelberg, Germany, 2012, 131, pp. 25-61.
[http://dx.doi.org/10.1007/10_2012_138]
[59]
Gibbons, S.; Oluwatuyi, M.; Kaatz, G.W. A novel inhibitor of multidrug efflux pumps in Staphylococcus aureus. J. Antimicrob. Chemother., 2003, 51(1), 13-17.
[http://dx.doi.org/10.1093/jac/dkg044] [PMID: 12493782]
[60]
Rezzonico, F.; Smits, T.H.M.; Duffy, B. Detection of AI-2 receptors in genomes of Enterobacteriaceae suggests a role of type-2 quorum sensing in closed ecosystems. Sensors (Basel), 2012, 12(5), 6645-6665.
[http://dx.doi.org/10.3390/s120506645] [PMID: 22778662]
[61]
Taga, M.E.; Semmelhack, J.L.; Bassler, B.L. The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium. Mol. Microbiol., 2001, 42(3), 777-793.
[http://dx.doi.org/10.1046/j.1365-2958.2001.02669.x] [PMID: 11722742]

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