Skip to content
2000
Volume 21, Issue 17
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background and Objectives

is a foodborne pathogen that is a major concern for global health. Flagellin (FliC) is an essential protein in for both motility and virulence and is a key component of flagella. Hence, focusing on FliC protein is a promising strategy for developing new anti- agents. a medicinal plant, shows promising antimicrobial properties. Thus, this study explores the therapeutic potential of against FliC protein using computational methods in comparison to the standard antibiotic ciprofloxacin.

Methods

Molecular docking simulation was performed to evaluate the binding affinity and interaction pattern of bioactive compounds present in and ciprofloxacin against FliC protein. This study also analysed protein stability and dynamics studies of the apoprotein, ciprofloxacin, kesselringine, and gloriosine complexes using molecular dynamic (MD) simulation. The MMGBSA method computed binding free energies.

Results

Through docking simulations, it was found that gloriosine and kesselringine have strong binding affinity with FliC protein, similar to ciprofloxacin. MD simulation showed consistent protein-ligand complexes during the entire simulation. The MMGBSA analysis confirmed the positive interactions observed in the docking results, showing binding free energies similar to ciprofloxacin.

Conclusion

This study suggests that the phytocompounds of shows promising therapeutic potential as a source for creating anti- agents that target FliC protein. These results suggest that may have therapeutic potential against infections and should be further studied through and experiments.

Loading

Article metrics loading...

/content/journals/lddd/10.2174/0115701808334616240822055800
2024-08-28
2025-06-20
Loading full text...

Full text loading...

References

  1. MajowiczS.E. MustoJ. ScallanE. AnguloF.J. KirkM. O’BrienS.J. JonesT.F. FazilA. HoekstraR.M. The global burden of nontyphoidal Salmonella gastroenteritis.Clin. Infect. Dis.201050688288910.1086/650733 20158401
    [Google Scholar]
  2. EngS.K. PusparajahP. Ab MutalibN.S. SerH-L. ChanK-G. LeeL-H. Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance.Front. Life Sci.20158328429310.1080/21553769.2015.1051243
    [Google Scholar]
  3. ChenH.M. WangY. SuL.H. ChiuC.H. Nontyphoid salmonella infection: Microbiology, clinical features, and antimicrobial therapy.Pediatr. Neonatol.201354314715210.1016/j.pedneo.2013.01.010 23597525
    [Google Scholar]
  4. GewirtzA.T. SimonP.O.Jr SchmittC.K. TaylorL.J. HagedornC.H. O’BrienA.D. NeishA.S. MadaraJ.L. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response.J. Clin. Invest.200110719910910.1172/JCI10501 11134185
    [Google Scholar]
  5. TsaiM.H. HuangY.C. LinT.Y. HuangY.L. KuoC.C. ChiuC.H. Reappraisal of parenteral antimicrobial therapy for nontyphoidal Salmonella enteric infection in children.Clin. Microbiol. Infect.201117230030510.1111/j.1469‑0691.2010.03230.x 20384700
    [Google Scholar]
  6. JacobJ.J. PragasamA.K. VasudevanK. VeeraraghavanB. KangG. JohnJ. NagvekarV. MutrejaA. Salmonella Typhi acquires diverse plasmids from other Enterobacteriaceae to develop cephalosporin resistance.Genomics202111342171217610.1016/j.ygeno.2021.05.003 33965548
    [Google Scholar]
  7. PrattM. ForbesJ.D. KnoxN.C. BernsteinC.N. Van DomselaarG. Microbiome-mediated immune signaling in inflammatory bowel disease and colorectal cancer: Support from meta-omics data.Front. Cell Dev. Biol.2021971660410.3389/fcell.2021.716604 34869308
    [Google Scholar]
  8. HuenJ. YanZ. IwashkiwJ. DubeyS. GimenezM.C. OrtizM.E. PatelS.V. JonesM.D. RiaziA. TerebiznikM. BabaeiS. ShahinasD. A novel single domain antibody targeting flic flagellin of salmonella enterica for effective inhibition of host cell invasion.Front. Microbiol.201910266510.3389/fmicb.2019.02665 31849856
    [Google Scholar]
  9. SzilagyiA. GersonM. MendelsonJ. YusufN.A. Salmonella infections complicating inflammatory bowel disease.J. Clin. Gastroenterol.19857325125510.1097/00004836‑198506000‑00013 4020084
    [Google Scholar]
  10. ZhaL. GarrettS. SunJ. Salmonella infection in chronic inflammation and gastrointestinal cancer.Diseases2019712810.3390/diseases7010028 30857369
    [Google Scholar]
  11. GradelK.O. NielsenH.L. SchønheyderH.C. EjlertsenT. KristensenB. NielsenH. Increased short- and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis.Gastroenterology2009137249550110.1053/j.gastro.2009.04.001 19361507
    [Google Scholar]
  12. YamaguchiT. TomaS. TeraharaN. MiyataT. AshiharaM. MinaminoT. NambaK. KatoT. Structural and functional comparison of salmonella flagellar filaments composed of FljB and FliC.Biomolecules202010224610.3390/biom10020246 32041169
    [Google Scholar]
  13. CummingsL.A. WilkersonW.D. BergsbakenT. CooksonB.T. In vivo, fliC expression by Salmonella enterica serovar Typhimurium is heterogeneous, regulated by ClpX, and anatomically restricted.Mol. Microbiol.200661379580910.1111/j.1365‑2958.2006.05271.x 16803592
    [Google Scholar]
  14. DuckW.L. WalterM.R. NovakJ. KellyD. TomasiM. CongY. ElsonC.O. Isolation of flagellated bacteria implicated in Crohnʼs disease.Inflamm. Bowel Dis.200713101191120110.1002/ibd.20237 17712838
    [Google Scholar]
  15. IvisonS.M. HimmelM.E. HardenbergG. WarkP.A.J. KifayetA. LevingsM.K. SteinerT.S. TLR5 is not required for flagellin-mediated exacerbation of DSS colitis.Inflamm. Bowel Dis.201016340140910.1002/ibd.21097 19774646
    [Google Scholar]
  16. SchultzB.M. PaduroC.A. SalazarG.A. Salazar-EchegaraiF.J. SebastiánV.P. RiedelC.A. KalergisA.M. Alvarez-LobosM. BuenoS.M. A potential role of Salmonella infection in the onset of inflammatory bowel diseases.Front. Immunol.2017819110.3389/fimmu.2017.00191 28293241
    [Google Scholar]
  17. WinterS.E. ThiennimitrP. NuccioS.P. HanedaT. WinterM.G. WilsonR.P. RussellJ.M. HenryT. TranQ.T. LawhonS.D. GomezG. BevinsC.L. RüssmannH. MonackD.M. AdamsL.G. BäumlerA.J. Contribution of flagellin pattern recognition to intestinal inflammation during Salmonella enterica serotype typhimurium infection.Infect. Immun.20097751904191610.1128/IAI.01341‑08 19237529
    [Google Scholar]
  18. NairV. KumarR. SinghS. GuptaY.K. Investigation into the anti-inflammatory and antigranuloma activity of Colchicum luteum Baker in experimental models.Inflammation201235388188810.1007/s10753‑011‑9389‑2 21938464
    [Google Scholar]
  19. AdhikariP.P. PaulS.B. History of Indian traditional medicine: A medical inheritance.Asian J. Pharm. Clin. Res.2018111421426
    [Google Scholar]
  20. AhmadS. HamdardJ. Analysis and regulation of traditional indian unani medicines.J. AOAC Int.2020103360760810.5740/jaoacint.19‑0320 31623700
    [Google Scholar]
  21. AhmadB. KhanH. BashirS. AliM. Antimicrobial bioassay of colchicum luteum baker.J. Enzyme Inhib. Med. Chem.200621676576910.1080/14756360600900547 17252951
    [Google Scholar]
  22. HuangW. WangY. TianW. CuiX. TuP. LiJ. ShiS. LiuX. Biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents derived from medicinal plants.Antibiotics 20221110138010.3390/antibiotics11101380 36290037
    [Google Scholar]
  23. AkhtarN. RashidA. MuradW. BergmeierE. Diversity and use of ethno-medicinal plants in the region of Swat, North Pakistan.J. Ethnobiol. Ethnomed.2013912510.1186/1746‑4269‑9‑25 23587127
    [Google Scholar]
  24. OthmanL. SleimanA. Abdel-MassihR.M. Antimicrobial activity of polyphenols and alkaloids in middle eastern plants.Front. Microbiol.20191091110.3389/fmicb.2019.00911 31156565
    [Google Scholar]
  25. MisraA. ChaudharyM.K. SinghS.P. TripathiD. BarikS.K. SrivastavaS. Docking experiments suggest that gloriosine has microtubule-targeting properties similar to colchicine.Sci. Rep.2023131485410.1038/s41598‑023‑31187‑6 36964265
    [Google Scholar]
  26. RatherR.A. BanoH. PerveenK. BukhariN.A. PadderS.A. BabaT.R. QureshiA. KhanN.A. KhanA.H. SamaraweeraH. Antifungal potential of Colchicum luteum and determination of colchicine content using HPLC for application as a fungicide.J. King Saud Univ. Sci.202234310187610.1016/j.jksus.2022.101876
    [Google Scholar]
  27. AnzengruberF. GrafV. HafnerJ. MeienbergerN. GuenovaE. DummerR. Efficacy and safety of colchicine in inflammatory skin diseases: A retrospective, monocentric study in a large tertiary center.J. Dermatolog. Treat.202132110410910.1080/09546634.2019.1690621 31694429
    [Google Scholar]
  28. WechslerB. Colchicine and Behçet’s disease: Finally recognized effectiveness!Rev. Med. Interne200223435535610.1016/S0248‑8663(02)00569‑6 11980310
    [Google Scholar]
  29. FalahianshafieiS. AkhtariJ. DavoodiA. Evaluation of anticancer effect of Colchicum autumnale L. Corm lll.BMC Complement Med. Ther202323
    [Google Scholar]
  30. DavisM.W. WasonS. DiGiacintoJ.L. Colchicine-antimicrobial drug interactions: What pharmacists need to know in treating gout.Consult Pharm.201328317618310.4140/TCP.n.2013.176 23462027
    [Google Scholar]
  31. GaikwadV. SabaleV. KhadeB. Synthesis, characterization, in silico and in vitro studies of transition metal complexes with biologically active ligand as antigout agent colchicine.Int. J. Pharm. Sci. Drug Res.202010711410.25004/IJPSDR.2020.120203
    [Google Scholar]
  32. SubiramaniS. SundararajanS. GovindarajanS. SadasivamV. GanesanP.K. PackiarajG. ManickamV. ThiruppathiS.K. RamalingamS. NarayanasamyJ. Optimized in vitro micro-tuber production for colchicine biosynthesis in Gloriosa superba L. and its anti-microbial activity against Candida albicans.Plant Cell Tissue Organ Cult.2019139117719010.1007/s11240‑019‑01675‑7
    [Google Scholar]
  33. ShafiqueI. RafiqM. RanaN.F. MenaaF. AlmalkiF. AljuaidA. AlnasserS.M. AlotaibiA.S. MasoodM.B.E. TanweerT. Computational evaluation of efflux pump homologues and lignans as potent inhibitors against multidrug-resistant Salmonella typhi.PLoS One2024196e030328510.1371/journal.pone.0303285 38917154
    [Google Scholar]
  34. RashidF. JavaidA. Mahmood-ur-Rahman; Ashfaq, U.; Sufyan, M.; Alshammari, A.; Alharbi, M.; Nisar, M.; Khurshid, M. Integrating pharmacological and computational approaches for the phytochemical analysis of syzygium cumini and its anti-diabetic potential.Molecules20222717573410.3390/molecules27175734 36080496
    [Google Scholar]
  35. OyedaraO.O. FadareO.A. Franco-FríasE. HerediaN. GarcíaS. Computational assessment of phytochemicals of medicinal plants from Mexico as potential inhibitors of Salmonella enterica efflux pump AcrB protein.J. Biomol. Struct. Dyn.20234151776178910.1080/07391102.2021.2024261 34996337
    [Google Scholar]
  36. AzmalM. HossenM.S. ShohanM.N.H. TaquiR. MalikA. GhoshA. A computational approach to identify phytochemicals as potential inhibitor of acetylcholinesterase: Molecular docking, ADME profiling and molecular dynamics simulations.PLoS One2024196e030449010.1371/journal.pone.0304490 38833492
    [Google Scholar]
  37. KumariR. RathiR. PathakS.R. DalalV. Computational investigation of potent inhibitors against YsxC: structure-based pharmacophore modeling, molecular docking, molecular dynamics, and binding free energy.J. Biomol. Struct. Dyn.202341393094110.1080/07391102.2021.2015446 34913841
    [Google Scholar]
  38. BermanH.M. BattistuzT. BhatT.N. The protein data bank Acta Crystallogr. D Biol. Crystallogr200258
    [Google Scholar]
  39. MorrisG.M. RuthH. LindstromW. Software news and updates AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.J. Comput. Chem.200930
    [Google Scholar]
  40. Vivek-AnanthR.P. MohanrajK. SahooA.K. SamalA. IMPPAT 2.0: An enhanced and expanded phytochemical atlas of indian medicinal plants.ACS Omega2023898827884510.1021/acsomega.3c00156 36910986
    [Google Scholar]
  41. KimS. Exploring chemical information in PubChem.Curr. Protoc.202118e21710.1002/cpz1.217 34370395
    [Google Scholar]
  42. DainaA. MichielinO. ZoeteV. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.Sci. Rep.2017714271710.1038/srep42717 28256516
    [Google Scholar]
  43. BanerjeeP. EckertA.O. SchreyA.K. PreissnerR. ProTox-II: A webserver for the prediction of toxicity of chemicals.Nucleic Acids Res.201846W1W257W26310.1093/nar/gky318 29718510
    [Google Scholar]
  44. O’BoyleN.M. BanckM. JamesC.A. MorleyC. VandermeerschT. HutchisonG.R. Open Babel: An open chemical toolbox.J. Cheminform.2011313310.1186/1758‑2946‑3‑33 21982300
    [Google Scholar]
  45. DeepasreeK. SubhashreeV. Molecular docking and dynamic simulation studies of terpenoid compounds against phosphatidylinositol-specific phospholipase c from *listeria monocytogenes.Inform. Med. Unlocked202339
    [Google Scholar]
  46. Mohammed Naveez ValathoorSV In silico analysis of structure and function of hypothetical proteins in *Salmonella typhimurium* (SL1344).Res. J. Pharm. Technol.202472024
    [Google Scholar]
  47. ElkhattabiL. ZouhdiS. MoussetadF. KettaniA. BarakatA. SaileR. Molecular docking analysis of PPARγ with phytochemicals from Moroccan medicinal plants.Bioinformation202319779580510.6026/97320630019795 37901293
    [Google Scholar]
  48. KushwahaP.P. SinghA.K. BansalT. YadavA. PrajapatiK.S. ShuaibM. KumarS. Identification of natural inhibitors against sars-cov-2 drugable targets using molecular docking, molecular dynamics simulation, and MM-PBSA approach.Front. Cell. Infect. Microbiol.20211173028810.3389/fcimb.2021.730288 34458164
    [Google Scholar]
  49. Biovia discovery studio® 2020: Comprehensive modeling and simulations for life sciences datasheet. Dassault systemes: The 3D experience company.2020Available from: https://www.3ds.com/fileadmin/PRODUCTS-SERVICES/BIOVIA/PDF/biovia-discovery-studio-whats-new-2020.pdf
  50. PettersenE.F. GoddardT.D. HuangC.C. CouchG.S. GreenblattD.M. MengE.C. FerrinT.E. UCSF Chimera—A visualization system for exploratory research and analysis.J. Comput. Chem.200425131605161210.1002/jcc.20084 15264254
    [Google Scholar]
  51. DethlefsenL. HuseS. SoginM.L. RelmanD.A. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.PLoS Biol.2008611e28010.1371/journal.pbio.0060280 19018661
    [Google Scholar]
  52. Van Der SpoelD. LindahlE. HessB. GroenhofG. MarkA.E. BerendsenH.J.C. GROMACS: Fast, flexible, and free.J. Comput. Chem.200526161701171810.1002/jcc.20291 16211538
    [Google Scholar]
  53. Hephzibah CathrynR. George Priya DossC. Comparative molecular dynamics simulation of apo and holo forms of the P53 mutant C176F: A structural perspective.J. Taibah Univ. Sci.2024181229745710.1080/16583655.2023.2297457
    [Google Scholar]
  54. VanommeslaegheK. HatcherE. AcharyaC. KunduS. ZhongS. ShimJ. DarianE. GuvenchO. LopesP. VorobyovI. MackerellA.D. Jr CHARMM general force field: A force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields.J. Comput. Chem.201031467169010.1002/jcc.21367 19575467
    [Google Scholar]
  55. ZoeteV. CuendetM.A. GrosdidierA. MichielinO. SwissParam: A fast force field generation tool for small organic molecules.J. Comput. Chem.201132112359236810.1002/jcc.21816 21541964
    [Google Scholar]
  56. AndersenH.C. Molecular dynamics simulations at constant pressure and/or temperature.J. Chem. Phys.19807242384239310.1063/1.439486
    [Google Scholar]
  57. BerendsenH.J.C. PostmaJ.P.M. van GunsterenW.F. DiNolaA. HaakJ.R. Molecular dynamics with coupling to an external bath.J. Chem. Phys.19848183684369010.1063/1.448118
    [Google Scholar]
  58. GopikrishnanM. George Priya DossC. Molecular docking and dynamic approach to screen the drug candidate against the Imipenem-resistant CarO porin in Acinetobacter baumannii.Microb. Pathog.202317710604910.1016/j.micpath.2023.106049 36858184
    [Google Scholar]
  59. Callil-SoaresP.H. BiasiL.C.K. Pessoa FilhoP.A. Effect of preprocessing and simulation parameters on the performance of molecular docking studies.J. Mol. Model.202329825110.1007/s00894‑023‑05637‑x 37452150
    [Google Scholar]
  60. SargsyanK. GrauffelC. LimC. How molecular size impacts rmsd applications in molecular dynamics simulations.J. Chem. Theory Comput.20171341518152410.1021/acs.jctc.7b00028 28267328
    [Google Scholar]
  61. TurnerP. XMGRACE, Version 5.1. 19. Center for Coastal and Land-Margin Research.BeavertonOregon Graduate Institute of Science and Technology2005
    [Google Scholar]
  62. KumariR. KumarV. DhankharP. DalalV. Promising antivirals for PLpro of SARS-CoV-2 using virtual screening, molecular docking, dynamics, and MMPBSA.J. Biomol. Struct. Dyn.202341104650466610.1080/07391102.2022.2071340 35510600
    [Google Scholar]
  63. BelloM. Evaluation of structural and thermodynamic insight of ERβ with DPN and derivatives through MMGBSA/MMPBSA methods.Steroids202420110933410.1016/j.steroids.2023.109334 37949336
    [Google Scholar]
  64. JawarkarR.D. SharmaP. JainN. GandhiA. MukerjeeN. Al-MutairiA.A. ZakiM.E.A. Al-HussainS.A. SamadA. MasandV.H. GhoshA. BakalR.L. QSAR, molecular docking, MD simulation and MMGBSA calculations approaches to recognize concealed pharmacophoric features requisite for the optimization of ALK tyrosine kinase inhibitors as anticancer leads.Molecules20222715495110.3390/molecules27154951 35956900
    [Google Scholar]
  65. LipinskiC.A. Lead- and drug-like compounds: The rule-of-five revolution.Drug Discov. Today. Technol.20041433734110.1016/j.ddtec.2004.11.007 24981612
    [Google Scholar]
  66. PeeleK.A. IndiraM. SibyL. Phytochemical and bioactive potential of Gloriosa Superba L.In: Biomolecules and Pharmacology of Medicinal Plants.Academia202310.1201/9781003284468‑31
    [Google Scholar]
  67. GoelB. DeyB. ChatterjeeE. TripathiN. BhardwajN. KumarS. GuruS.K. JainS.K. Antiproliferative potential of gloriosine: A lead for anticancer drug development.ACS Omega2022733289942900110.1021/acsomega.2c02688 36033689
    [Google Scholar]
  68. KumariR. DalalV. Identification of potential inhibitors for LLM of Staphylococcus aureus: Structure-based pharmacophore modeling, molecular dynamics, and binding free energy studies.J. Biomol. Struct. Dyn.202240209833984710.1080/07391102.2021.1936179 34096457
    [Google Scholar]
  69. RathiR. KumariR. PathakS.R. DalalV. Promising antibacterials for LLM of Staphylococcus aureus using virtual screening, molecular docking, dynamics, and MMPBSA.J. Biomol. Struct. Dyn.202341157277728910.1080/07391102.2022.2119278 36073371
    [Google Scholar]
  70. IslamM.A. HossainM.S. HasnatS. ShuvoM.H. AkterS. MariaM.A. TahcinA. HossainM.A. HoqueM.N. In-silico study unveils potential phytocompounds in Andrographis paniculata against E6 protein of the high-risk HPV-16 subtype for cervical cancer therapy.Sci. Rep.20241411718210.1038/s41598‑024‑65112‑2 39060289
    [Google Scholar]
  71. SwargiaryA. MahmudS. SalehM.A. Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: An in silico approach to combat COVID-19.J. Biomol. Struct. Dyn.20224052067208110.1080/07391102.2020.1835729 33089730
    [Google Scholar]
  72. AlhamhoomY. HaniU. BennaniF.E. RahmanN. RashidM.A. AbbasM.N. RastrelliL. Identification of new drug target in Staphylococcus lugdunensis by subtractive genomics analysis and their inhibitors through molecular docking and molecular dynamic simulation studies.Bioengineering 20229945110.3390/bioengineering9090451 36134997
    [Google Scholar]
  73. AshfaqF. BarkatM.A. AhmadT. HassanM.Z. AhmadR. BarkatH. Idreesh KhanM. Saad AlhodiebF. AsiriY.I. SiddiquiS. Phytocompound screening, antioxidant activity and molecular docking studies of pomegranate seed: A preventive approach for SARS-CoV-2 pathogenesis.Sci. Rep.20231311706910.1038/s41598‑023‑43573‑1 37816760
    [Google Scholar]
  74. ElebijuO.F. OduseluG.O. OgunnupebiT.A. AjaniO.O. AdebiyiE. In silico design of potential small-molecule antibiotic adjuvants against salmonella typhimurium ortho acetyl sulphydrylase synthase to address antimicrobial resistance.Pharmaceuticals202417554310.3390/ph17050543 38794114
    [Google Scholar]
  75. MishraD. MauryaR.R. KumarK. MunjalN.S. BahadurV. SharmaS. SinghP. BahadurI. Structurally modified compounds of hydroxychloroquine, remdesivir and tetrahydrocannabinol against main protease of SARS-CoV-2, a possible hope for COVID-19: Docking and molecular dynamics simulation studies.J. Mol. Liq.202133511618510.1016/j.molliq.2021.116185 33879934
    [Google Scholar]
  76. KumariR. RathiR. PathakS.R. DalalV. Structural-based virtual screening and identification of novel potent antimicrobial compounds against YsxC of Staphylococcus aureus.J. Mol. Struct.2022125513247610.1016/j.molstruc.2022.132476
    [Google Scholar]
/content/journals/lddd/10.2174/0115701808334616240822055800
Loading
/content/journals/lddd/10.2174/0115701808334616240822055800
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test