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2000
Volume 21, Issue 6
  • ISSN: 1570-1646
  • E-ISSN: 1875-6247

Abstract

Background

Sepsis is defined as the extreme response of a body to an infection, leading to untimely death if left untreated. The human gut microbiome is characterized by the presence of several microorganisms in the gastrointestinal tract. This study provides insight into the potential therapeutic effects of a peptide present in the human gut microbiome that helps control sepsis.

Aims

This study aimed to explore the therapeutic application of a peptide from in the human gut microbiome as an alternative to MRSA, which causes severe, fatal diseases like sepsis. It also elucidates the peptide-protein interactions that enhance the efficacy of infection control and treatment.

Objectives

We aimed to investigatethe interactions between protein-peptide and protein-drug complexes through analyses.

Methods

Molecular docking was performed using PyRx and HADDOCK tools. Next, we performed molecular simulation studies using GROMACS v2020.6 at different physiological pH values of 4, 6, and 7.4. Stability, compactness, and binding energies were analyzed usingparameters such as RMSD, Rg, and MMPBSA, among other parameters.

Results

We observed stability on docking between Plantaricin KL-1Y, an effective bacteriocin from (organism from gut microbiome), and PBP2a from (causative organism of sepsis). This was indicated by a binding affinity of -13.4 kcal/mol, higher than that of PBP2a-FDA-approved drug (-8 kcal/mol). The MMPBSA results of the PBP2a-Plantaricin KL-1Y complex showed a significantly higher binding affinity at pH 7.4 of -228.451 kcal/mol in comparison to -69.5747 kcal/mol for the PBP2a-Ceftaroline fosamil complex.

Conclusion

These results indicate the possible use of a peptide from the human gut as a potential therapeutic agent against infection.

© 2024 Bentham Science Publishers
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2025-01-06
2025-07-22

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References

  1. DanielskiL.G. GiustinaA.D. BonfanteS. BarichelloT. PetronilhoF. The NLRP3 Inflammasome and Its Role in Sepsis Development.Inflammation2020431243110.1007/s10753‑019‑01124‑9 31741197
     [Google Scholar]
  2. TangK.W.K. MillarB.C. MooreJ.E. Antimicrobial Resistance (AMR).Br. J. Biomed. Sci.2023801138710.3389/bjbs.2023.11387 37448857
     [Google Scholar]
  3. MinasyanH. Sepsis: mechanisms of bacterial injury to the patient.Scand. J. Trauma Resusc. Emerg. Med.20192711910.1186/s13049‑019‑0596‑4 30764843
     [Google Scholar]
  4. RhodesA. EvansL.E. AlhazzaniW. LevyM.M. AntonelliM. FerrerR. KumarA. SevranskyJ.E. SprungC.L. NunnallyM.E. RochwergB. RubenfeldG.D. AngusD.C. AnnaneD. BealeR.J. BellinghanG.J. BernardG.R. ChicheJ.D. CoopersmithC. De BackerD.P. FrenchC.J. FujishimaS. GerlachH. HidalgoJ.L. HollenbergS.M. JonesA.E. KarnadD.R. KleinpellR.M. KohY. LisboaT.C. MachadoF.R. MariniJ.J. MarshallJ.C. MazuskiJ.E. McIntyreL.A. McLeanA.S. MehtaS. MorenoR.P. MyburghJ. NavalesiP. NishidaO. OsbornT.M. PernerA. PlunkettC.M. RanieriM. SchorrC.A. SeckelM.A. SeymourC.W. ShiehL. ShukriK.A. SimpsonS.Q. SingerM. ThompsonB.T. TownsendS.R. Van der PollT. VincentJ.L. WiersingaW.J. ZimmermanJ.L. DellingerR.P. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.Crit. Care Med.201745348655210.1097/CCM.0000000000002255 28098591
     [Google Scholar]
  5. FergestadM.E. StamsåsG.A. Morales AngelesD. SalehianZ. WastesonY. KjosM. Penicillin-binding protein PBP2a provides variable levels of protection toward different β-lactams in Staphylococcus aureus RN4220.MicrobiologyOpen202098e105710.1002/mbo3.1057 32419377
     [Google Scholar]
  6. RinninellaE. RaoulP. CintoniM. FranceschiF. MiggianoG.A.D. GasbarriniA. MeleM.C. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases.Microorganisms2019711410.3390/microorganisms7010014 30634578
     [Google Scholar]
  7. ThursbyE. JugeN. Introduction to the human gut microbiota.Biochem. J.2017474111823183610.1042/BCJ20160510 28512250
     [Google Scholar]
  8. BullM.J. PlummerN.T. Part 1: The Human Gut Microbiome in Health and Disease.Integr. Med. (Encinitas)20141361722 26770121
     [Google Scholar]
  9. DempseyE. CorrS.C. Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives.Front. Immunol.20221384024510.3389/fimmu.2022.840245 35464397
     [Google Scholar]
  10. WangL. WangN. ZhangW. ChengX. YanZ. ShaoG. WangX. WangR. FuC. Therapeutic peptides: current applications and future directions.Signal Transduct. Target. Ther.2022714810.1038/s41392‑022‑00904‑4 35165272
     [Google Scholar]
  11. RumjuankiatK. PerezR.H. PilasombutK. KeawsompongS. ZendoT. SonomotoK. NitisinprasertS. Purification and characterization of a novel plantaricin, KL-1Y, from Lactobacillus plantarum KL-1.World J. Microbiol. Biotechnol.201531698399410.1007/s11274‑015‑1851‑0 25862353
     [Google Scholar]
  12. KimS. ChenJ. ChengT. GindulyteA. HeJ. HeS. LiQ. ShoemakerB.A. ThiessenP.A. YuB. ZaslavskyL. ZhangJ. BoltonE.E. PubChem 2023 update.Nucleic Acids Res.202351D1D1373D138010.1093/nar/gkac956 36305812
     [Google Scholar]
  13. PrabhavathiH. DasegowdaK.R. RenukanandaK.H. KarunakarP. LingarajuK. Raja NaikaH. Molecular docking and dynamic simulation to identify potential phytocompound inhibitors for EGFR and HER2 as anti-breast cancer agents.J. Biomol. Struct. Dyn.202240104713472410.1080/07391102.2020.1861982 33345701
     [Google Scholar]
  14. ManjunathA. ChinmayiG.V.A. RenganathanS. ChandramohanV. SabatS. Antimicrobial activity of Geranyl acetate against cell wall synthesis proteins of P. aeruginosa and S. aureus using molecular docking and simulation.J. Biomol. Struct. Dyn.2023121 37199273
     [Google Scholar]
  15. BatemanA. MartinM-J. OrchardS. MagraneM. AhmadS. AlpiE. Bowler-BarnettE.H. BrittoR. Bye-A-JeeH. CukuraA. DennyP. DoganT. EbenezerT.G. FanJ. GarmiriP. da Costa GonzalesL.J. Hatton-EllisE. HusseinA. IgnatchenkoA. InsanaG. IshtiaqR. JoshiV. JyothiD. KandasaamyS. LockA. LucianiA. LugaricM. LuoJ. LussiY. MacDougallA. MadeiraF. MahmoudyM. MishraA. MoulangK. NightingaleA. PundirS. QiG. RajS. RaposoP. RiceD.L. SaidiR. SantosR. SperettaE. StephensonJ. TotooP. TurnerE. TyagiN. VasudevP. WarnerK. WatkinsX. ZaruR. ZellnerH. BridgeA.J. AimoL. Argoud-PuyG. AuchinclossA.H. AxelsenK.B. BansalP. BaratinD. Batista NetoT.M. BlatterM-C. BollemanJ.T. BoutetE. BreuzaL. GilB.C. Casals-CasasC. EchioukhK.C. CoudertE. CucheB. de CastroE. EstreicherA. FamigliettiM.L. FeuermannM. GasteigerE. GaudetP. GehantS. GerritsenV. GosA. GruazN. HuloC. Hyka-NouspikelN. JungoF. KerhornouA. Le MercierP. LieberherrD. MassonP. MorgatA. MuthukrishnanV. PaesanoS. PedruzziI. PilboutS. PourcelL. PouxS. PozzatoM. PruessM. RedaschiN. RivoireC. SigristC.J.A. SonessonK. SundaramS. WuC.H. ArighiC.N. ArminskiL. ChenC. ChenY. HuangH. LaihoK. McGarveyP. NataleD.A. RossK. VinayakaC.R. WangQ. WangY. ZhangJ. UniProt: The universal protein knowledgebase in 2023.Nucleic Acids Res.202351D1D523D53110.1093/nar/gkac1052 36408920
     [Google Scholar]
  16. HonoratoR.V. KoukosP.I. Jiménez-GarcíaB. TsaregorodtsevA. VerlatoM. GiachettiA. RosatoA. BonvinA.M.J.J. Structural biology in the clouds: The WeNMR-EOSC ecosystem.Front. Mol. Biosci.2021872951310.3389/fmolb.2021.729513 34395534
     [Google Scholar]
  17. BorkotokyS. MuraliA. A computational assessment of pH-dependent differential interaction of T7 lysozyme with T7 RNA polymerase.BMC Struct. Biol.2018171710.1186/s12900‑017‑0077‑9 28545576
     [Google Scholar]
  18. de VriesS.J. van DijkM. BonvinA.M.J.J. The HADDOCK web server for data-driven biomolecular docking.Nat. Protoc.20105588389710.1038/nprot.2010.32 20431534
     [Google Scholar]
  19. MohankumarT. ChandramohanV. LalithambaH.S. JayarajR.L. KumaradhasP. SivanandamM. HundayG. VijayakumarR. BalakrishnanR. ManimaranD. ElangovanN. Design and Molecular dynamic Investigations of 7,8-Dihydroxyflavone Derivatives as Potential Neuroprotective Agents Against Alpha-synuclein.Sci. Rep.202010159910.1038/s41598‑020‑57417‑9 31953434
     [Google Scholar]
  20. OostenbrinkC. VillaA. MarkA.E. Van GunsterenW.F. A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force-field parameter sets 53A5 and 53A6.J. Comput. Chem.200425131656167610.1002/jcc.20090 15264259
     [Google Scholar]
  21. GordonJ.C. MyersJ.B. FoltaT. ShojaV. HeathL.S. OnufrievA.H. ++: a server for estimating pKas and adding missing hydrogens to macromolecules.Nucleic Acids Res.2005331W368-37110.1093/nar/gki464 15980491
     [Google Scholar]
  22. LaskowskiR.A. Jabłońska, J.; Pravda, L.; Vařeková, R.S.; Thornton, J.M. PDBsum: Structural summaries of PDB entries.Protein Sci.201827112913410.1002/pro.3289 28875543
     [Google Scholar]
  23. GangadharappaB.S. SharathR. RevanasiddappaP.D. ChandramohanV. BalasubramaniamM. VardhineniT.P. Structural insights of metallo-beta-lactamase revealed an effective way of inhibition of enzyme by natural inhibitors.J. Biomol. Struct. Dyn.202038133757377110.1080/07391102.2019.1667265 31514687
     [Google Scholar]
  24. KumariR. KumarR. LynnA. g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations.J. Chem. Inf. Model.20145471951196210.1021/ci500020m 24850022
     [Google Scholar]
  25. JanardhananJ. BouleyR. Martínez-CaballeroS. PengZ. Batuecas-MordilloM. MeiselJ.E. DingD. SchroederV.A. WolterW.R. MahasenanK.V. HermosoJ.A. MobasheryS. ChangM. The Quinazolinone Allosteric Inhibitor of PBP 2a Synergizes with Piperacillin and Tazobactam against Methicillin-Resistant Staphylococcus aureus.Antimicrob. Agents Chemother.2019635e026371810.1128/AAC.02637‑18 30858202
     [Google Scholar]
  26. ShirleyD.A.T. HeilE.L. JohnsonJ.K. Ceftaroline fosamil: a brief clinical review.Infect. Dis. Ther.2013229511010.1007/s40121‑013‑0010‑x 25134474
     [Google Scholar]
  27. VangoneA. BonvinA.M.J.J. Contacts-based prediction of binding affinity in protein–protein complexes.eLife20154e0745410.7554/eLife.07454 26193119
     [Google Scholar]
  28. RajagopalA. v, A.; Ramu, K.; Chandramohan, V.; Sabat, S. Investigative Study on the influence of Physiological pH on Choline TMA Lyase in P. vulgaris by Molecular Dynamics and Simulation.Res. J. Biotechnol.202318210411110.25303/1802rjbt1040111
     [Google Scholar]
  29. NguyenH.M. GraberC.J. Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?J. Antimicrob. Chemother.2010651243610.1093/jac/dkp377 19861337
     [Google Scholar]
  30. KashyapR. ShahA. DuttT. WieruszewskiP.M. AhdalJ. JainR. Treatments and limitations for methicillin-resistant Staphylococcus aureus: A review of current literature.World J. Clin. Infect. Dis.20199111010.5495/wjcid.v9.i1.1
     [Google Scholar]
  31. ChiangY.C. WongM.T.Y. EssexJ.W. Molecular Dynamics Simulations of Antibiotic Ceftaroline at the Allosteric Site of Penicillin-Binding Protein 2a (PBP2a).Isr. J. Chem.202060775476310.1002/ijch.202000012
     [Google Scholar]
  32. KalaloM.J. FatimawaliF. KalaloT. RambiC.I.J. Tea bioactive compounds as inhibitor of mrsa penicillin binding protein 2a (PBP2A): A molecular docking study.Jurnal Farmasi Medica/Pharmacy Medical Journal (PMJ)2021327010.35799/pmj.3.2.2020.32878
     [Google Scholar]
  33. HubbardR.E. Kamran HaiderM. eLS hydrogen bonds in proteins: Role and strength; John Wiley & Sons:Hoboken New Jersey2010301110.1002/9780470015902.a0003011.pub2
     [Google Scholar]
  34. WangC. GreeneD.A. XiaoL. QiR. LuoR. Recent Developments and Applications of the MMPBSA Method.Front. Mol. Biosci.201848710.3389/fmolb.2017.00087 29367919
     [Google Scholar]
  35. TamK. TorresV.J. Staphylococcus aureus secreted toxins and extracellular enzymes.Microbiol. Spectr.2019727.2.1610.1128/microbiolspec.GPP3‑0039‑201830873936
     [Google Scholar]
  36. MalikM. SubocT.M. TyagiS. SalzmanN. WangJ. YingR. TannerM.J. KakarlaM. BakerJ.E. WidlanskyM.E. Lactobacillus plantarum 299v supplementation improves vascular endothelial function and reduces inflammatory biomarkers in men with stable coronary artery disease.Circ. Res.201812391091110210.1161/CIRCRESAHA.118.313565 30355158
     [Google Scholar]
  37. WangH. XieY. ZhangH. JinJ. ZhangH. Quantitative proteomic analysis reveals the influence of plantaricin BM-1 on metabolic pathways and peptidoglycan synthesis in Escherichia coli K12.PLoS One2020154e023197510.1371/journal.pone.0231975 32324803
     [Google Scholar]
  38. Abdulhussain KareemR. RazaviS.H. Plantaricin bacteriocins: As safe alternative antimicrobial peptides in food preservation: A review.J. Food Saf.2020401e1273510.1111/jfs.12735
     [Google Scholar]
  39. MontvilleT.J. BrunoM.E.C. Evidence that dissipation of proton motive force is a common mechanism of action for bacteriocins and other antimicrobial proteins.Int. J. Food Microbiol.1994241-2537410.1016/0168‑1605(94)90106‑6 7703030
     [Google Scholar]
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Study on the Role of Human Gut Microbiome in Controlling MRSA-Induced Sepsis Using Proteomics Tool
Curr. Proteomics 21, 795 (2024); https://doi.org/10.2174/0115701646347818241231081829
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  • Article Type:     Research Article
Keyword(s): GROMACS; Gut microbiome; HADDOCK; MRSA; plantaricin KL-1Y; sepsis

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