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Antibacterial and In Silico Evaluation of β-lactamase Inhibitory Potential of Pinus sylvestris L. (Scots Pine) Essential Oil

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Proceedings of the National Academy of Sciences, India Section B: Biological Sciences Aims and scope Submit manuscript

Abstract

Antibiotic resistance remains one of the global challenges that needs urgent attention, including finding alternative treatment options to conventional antibiotics and reversing resistance. Pinus sylvestris L. (Pinaceae) essential oil (EO) has several biological properties. In this study, the EO of P. sylvestris was extracted by hydro-distillation method, and twenty-six chemical constituents of the EO identified by gas chromatography-mass spectrophotometry were screened as potential inhibitors of β-lactamase in silico by molecular docking. Antibacterial activity of the EO against thirteen bacterial isolates was further evaluated. Terpineol was identified as the major phytoconstituent of the P. sylvestris needles EO. From the docking analysis, benzene, 1,3-bis(3-phenoxyphenoxy) and dichloroacetic acid, 1-adamantylmethyl ester showed good inhibitory potentials against AmpC and OXA-23 β-lactamase, respectively, binding to the important catalytic serine residues (Ser64 and Ser79, respectively) with lower binding affinity energies (benzene, 1,3-bis(3-phenoxyphenoxy) =  −10.1 kcal/mol and dichloroacetic acid, 1-adamantylmethyl ester = −8.4 kcal/mol) compared to the FDA-approved β-lactamase inhibitor, avibactam (−6.5 and −6.6 kcal/mol for AmpC and OXA23 β-lactamase, respectively). The EO inhibited the growth of all the tested bacteria. Klebsiella pneumoniae and Micrococcus luteus were the most susceptible bacteria with an inhibition zone (ZI) of 24 mm each, while the ZI obtained for Proteus vulgaris was the lowest (ZI = 8 mm). The results obtained in this study showed that EO of P. sylvestris has potential as a treatment option for broad-spectrum bacterial infections and in the management of β-lactamase-related antibiotic resistance.

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References

  1. Öztürk H, Ozkirimli E, Özgür A (2015) Classification of beta-lactamases and penicillin binding proteins using ligand-centric network models. PLoS ONE 10(2):e0117874. https://doi.org/10.1371/journal.pone.0117874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Munita JM, Arias CA (2016) Mechanisms of antibiotic resistance. Microbiol Spectr 4(2):4–2. https://doi.org/10.1128/microbiolspec.VMBF-0016-2015

    Article  CAS  Google Scholar 

  3. Coutinho HDM, Matias EFF, Santos KKA, Tintino SR, Souza CES, Guedes GMM, Santos FAD, Costa JGM, Falcão-SilvaIqueira-Júnior VSJP (2010) Enhancement of the norfloxacin antibiotic activity by gaseous contact with the essential oil of Croton zehntneri. J Young Pharm 2(4):362–364. https://doi.org/10.4103/0975-1483.71625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Almeida RS, Freitas PR, Araújo ACJ, Alencar Menezes IR, Santos EL, Tintino SR, Moura TF, Ferreira VA, Silva ACA, Silva LE, do Amaral W, (2020) GC-MS profile and enhancement of antibiotic activity by the essential oil of Ocotea odorifera and safrole: Inhibition of Staphylococcus aureus efflux pumps. Antibiotics 9(5):247. https://doi.org/10.3390/antibiotics9050247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jin J, Zhang JY, Guo N, Sheng H, Li L, Liang JC, Wang XL, Li Y, Liu MY, Wu XP, Yu L (2010) Farnesol, a potential efflux pump inhibitor in Mycobacterium smegmatis. Molecules 15(11):7750–7762. https://doi.org/10.3390/molecules15117750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Veras HN, Rodrigues FF, Botelho MA, Menezes IR, Coutinho HD, Costa JG (2017) Enhancement of aminoglycosides and β-lactams antibiotic activity by essential oil of Lippia sidoides Cham. and the thymol. Arab J Chem 10:S2790–S2795. https://doi.org/10.1016/j.arabjc.2013.10.030

    Article  CAS  Google Scholar 

  7. Dhara L, Tripathi A (2013) Antimicrobial activity of eugenol and cinnamaldehyde against extended spectrum beta lactamase producing enterobacteriaceae by in vitro and molecular docking analysis. Eur J Integr Med 5(6):527–536. https://doi.org/10.1016/j.eujim.2013.08.005

    Article  Google Scholar 

  8. Fayemiwo KA, Adeleke MA, Okoro OP, Awojide SH, Awoniyi IO (2014) Larvicidal efficacies and chemical composition of essential oils of Pinus sylvestris and Syzygium aromaticum against mosquitoes. Asian Pac J Trop Biomed 4(1):30–34. https://doi.org/10.1016/S2221-1691(14)60204-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kızılarslan Ç, Sevg E (2013) Ethnobotanical uses of genus Pinus L. (Pinaceae) in Turkey. Indian J Tradit Knowl 12(2):209–220. http://nopr.niscair.res.in/handle/123456789/16860

  10. Sonibare OO, Olakunle K (2008) Chemical composition and antibacterial activity of the essential oil of Pinus caribaea from Nigeria. Afr J Biotechnol 7(14):2462–2464

    CAS  Google Scholar 

  11. Lin X, Li X, Lin X (2020) A review on applications of computational methods in drug screening and design. Molecules 25(6):1375. https://doi.org/10.3390/molecules25061375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Elyemni M, Louaste B, Nechad I, Elkamli T, Bouia A, Taleb M, Chaouch M, Eloutassi N (2019) Extraction of essential oils of Rosmarinus officinalis L. by two different methods: Hydrodistillation and microwave assisted hydrodistillation. Sci World J 2019: 6. https://doi.org/10.1155/2019/3659432

  13. Adams RP (2007) Identification of essential oil components by gas chromatography/ mass spectrometry, 4th edn. Allured Publ, Carol Stream, IL

    Google Scholar 

  14. Palzkill T (2018) Structural and mechanistic basis for extended-spectrum drug-resistance mutations in altering the specificity of TEM, CTX-M, and KPC β-lactamases. Front Mol Biosci 5:16. https://doi.org/10.3389/fmolb.2018.00016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Goldberg SD, Iannuccilli W, Nguyen T, Ju J, Cornish VW (2003) Identification of residues critical for catalysis in a class C β-lactamase by combinatorial scanning mutagenesis. Protein Sci 12(8):1633–1645. https://doi.org/10.1110/ps.0302903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Smith CA, Antunes NT, Stewart NK, Toth M, Kumarasiri M, Chang M, Mobashery S, Vakulenko SB (2013) Structural basis for carbapenemase activity of the OXA-23 β-lactamase from Acinetobacter baumannii. Chem Biol 20(9):1107–1115. https://doi.org/10.1016/j.chembiol.2013.07.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dallakyan S, Olso AJ (2015) Small-molecule library screening by docking with PyRx. In: Hempel J, Williams C, Hong C (eds) Chemical biology. methods in molecular biology, vol 1263. Humana Press, New York, NY pp 243–250. https://doi.org/10.1007/978-1-4939-2269-7_19

  18. Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7(1):1–13. https://doi.org/10.1038/srep42717

    Article  Google Scholar 

  19. Banerjee P, Eckert AO, Schrey AK, Preissner R (2018) ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 46(W1):W257–W263. https://doi.org/10.1093/nar/gky318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Akinpelu DA, Abioye EO, Aiyegoro OA, Akinpelu OF, Okoh AI (2015). Evaluation of antibacterial and antifungal properties of Alchornea laxiflora (Benth.) Pax. & Hoffman. Evid Based Complement Altern 2015. https://doi.org/10.1155/2015/684839

  21. Szmigielski R, Cieslak M, Rudziński KJ, Maciejewska B (2012) Identification of volatiles from Pinus silvestris attractive for Monochamus galloprovincialis using a SPME-GC/MS platform. Environ Sci Pollut Res 19(7):2860–2869. https://doi.org/10.1007/s11356-012-0792-5

    Article  CAS  Google Scholar 

  22. Badawy ME, Marei GIK, Rabea EI, Taktak NE (2019) Antimicrobial and antioxidant activities of hydrocarbon and oxygenated monoterpenes against some foodborne pathogens through in vitro and in silico studies. Pestic Biochem Physiol 158:185–200. https://doi.org/10.1016/j.pestbp.2019.05.008

    Article  CAS  PubMed  Google Scholar 

  23. Turchetti G, Garzoli S, Laghezza Masci V, Sabia C, Iseppi R, Giacomello P, Tiezzi A, Ovidi E (2020) Antimicrobial testing of Schinus molle (L.) leaf extracts and fractions followed by GC-MS investigation of biological active fractions. Molecules 25(8):1977. https://doi.org/10.3390/molecules25081977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Meng XY, Zhang HX, Mezei M, Cui M (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput-Aided Drug Des 7(2):146–157. https://doi.org/10.2174/157340911795677602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. González-Bello C, Rodríguez D, Pernas M, Rodríguez Á, Colchón E (2020) β-Lactamase inhibitors to restore the efficacy of antibiotics against superbugs. J Med Chem 63(5):1859–1881. https://doi.org/10.1021/acs.jmedchem.9b01279

    Article  CAS  PubMed  Google Scholar 

  26. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23(1–3):3–25. https://doi.org/10.1016/S0169-409X(96)00423-1

    Article  CAS  Google Scholar 

  27. Morak-Młodawska B, Jeleń M, Pluta K (2021) Phenothiazines modified with the pyridine ring as promising anticancer agents. Life 11(3):206. https://doi.org/10.3390/life11030206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Carrière F (2016) Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs. Biochimie 125:297–305. https://doi.org/10.1016/j.biochi.2015.11.016

    Article  CAS  PubMed  Google Scholar 

  29. Salamon I, Kryvtsova M, Bucko D, Tarawneh, AH (2021). Chemical characterization and antimicrobial activity of some essential oils after their industrial large-scale distillation. J Microbiol Biotechnol Food Sci 2021: 984–988. https://doi.org/10.15414/jmbfs.2018.8.3.965-969.

  30. Njoku IS, Rahman NU, Khan AM, Otunomo I, Asekun OT, Familoni OB, Ngozi C (2022) Chemical composition, antioxidant, and antibacterial activity of the essential oil from the leaves of Pinus sylvestris. Pac J Sci Technol 23(1):85–93

    Google Scholar 

  31. Mitić ZS, Jovanović B, Jovanović SČ, Mihajilov-Krstev T, Stojanović-Radić ZZ, Cvetković VJ, Mitrović, TL, Marin PD, Zlatković BK, Stojanović GS (2018) Comparative study of the essential oils of four Pinus species: Chemical composition, antimicrobial and insect larvicidal activity. Ind Crops Prod 111(2018):55–62

    Article  Google Scholar 

Download references

Acknowledgements

The authors appreciate the help of technologists at the Microbiology and Chemistry Department of Osun State University during the laboratory investigation.

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Authors and Affiliations

  1. Department of Chemical Engineering, Osun State University, Osogbo, Nigeria

    Kehinde A. Oyewole

  2. Department of Microbiology, Osun State University, Osogbo, Nigeria

    Omotayo O. Oyedara & Folasade M. Adeyemi

  3. Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, 66450, San Nicolás de los Garza, Nuevo León, Mexico

    Omotayo O. Oyedara

  4. Department of Pure and Applied Chemistry, Osun State University, Osogbo, Nigeria

    Shola H. Awojide & Mary O. Olawade

  5. Department of Microbiology, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria

    Oluwatayo E. Abioye

  6. Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Mexico

    Alfredo Juárez-Saldivar

  7. Applied Microbiology, Biotechnology and Nanotechnology Laboratory, Department of Microbiology, Edo University, Uzairue, Iyamho, Edo State, Nigeria

    Charles O. Adetunji

  8. Centro de Ciencia Genomica, Universidad Nacional Autonoma de Mexico (UNAM), Avenida Universidad S/N Chamilpa, Cuernavaca, Morelos, Mexico

    Temidayo O. Elufisan

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  1. Kehinde A. Oyewole
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Correspondence to Kehinde A. Oyewole or Omotayo O. Oyedara.

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Significance Statement: The study showed that P. sylvestris essential oil has broad-spectrum antibacterial activity and its phytoconstituents identified by GC-MS have the potential to inhibit β-lactamase enzymes.

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Oyewole, K.A., Oyedara, O.O., Awojide, S.H. et al. Antibacterial and In Silico Evaluation of β-lactamase Inhibitory Potential of Pinus sylvestris L. (Scots Pine) Essential Oil. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 93, 967–977 (2023). https://doi.org/10.1007/s40011-023-01490-3

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