Skip to main content
SpringerLink
Log in

A systems biology approach to investigate the antimicrobial activity of oleuropein

  • Applied Genomics & Systems Biotechnology - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Oleuropein and its hydrolysis products are olive phenolic compounds that have antimicrobial effects on a variety of pathogens, with the potential to be utilized in food and pharmaceutical products. While the existing research is mainly focused on individual genes or enzymes that are regulated by oleuropein for antimicrobial activities, little work has been done to integrate intracellular genes, enzymes and metabolic reactions for a systematic investigation of antimicrobial mechanism of oleuropein. In this study, the first genome-scale modeling method was developed to predict the system-level changes of intracellular metabolism triggered by oleuropein in Staphylococcus aureus, a common food-borne pathogen. To simulate the antimicrobial effect, an existing S. aureus genome-scale metabolic model was extended by adding the missing nitric oxide reactions, and exchange rates of potassium, phosphate and glutamate were adjusted in the model as suggested by previous research to mimic the stress imposed by oleuropein on S. aureus. The developed modeling approach was able to match S. aureus growth rates with experimental data for five oleuropein concentrations. The reactions with large flux change were identified and the enzymes of fifteen of these reactions were validated by existing research for their important roles in oleuropein metabolism. When compared with experimental data, the up/down gene regulations of 80% of these enzymes were correctly predicted by our modeling approach. This study indicates that the genome-scale modeling approach provides a promising avenue for revealing the intracellular metabolism of oleuropein antimicrobial properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Acquaviva R, Di Giacomo C, Sorrenti V et al (2012) Antiproliferative effect of oleuropein in prostate cell lines. Int J Oncol 41:31–38. doi:10.3892/ijo.2012.1428

    CAS  PubMed  Google Scholar 

  2. Becker SA, Feist AM, Mo ML et al (2007) Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox. Nat Protoc 2:727–738. doi:10.1038/nprot.2007.99

    Article  CAS  PubMed  Google Scholar 

  3. Becker SA, Palsson BØ (2005) Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation. BMC Microbiol 5:8. doi:10.1186/1471-2180-5-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Behnke K, Kaiser A, Zimmer I et al (2010) RNAi-mediated suppression of isoprene emission in poplar transiently impacts phenolic metabolism under high temperature and high light intensities: a transcriptomic and metabolomic analysis. Plant Mol Biol 74:61–75. doi:10.1007/s11103-010-9654-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bianco L, Alagna F, Baldoni L et al (2013) Proteome regulation during olea europaea fruit development. PLoS One. doi:10.1371/journal.pone.0053563

    Google Scholar 

  6. Briante R, La Cara F, Tunziello P, Febraio F, Nucci R (2001) Antioxidant activity of the main bioactive derivatives from oleuropeina hydrolysis by hyperthermophylic β-glucosidase. J Agric Food Chem 49:3198–3203

    Article  CAS  PubMed  Google Scholar 

  7. Carraro L, Fasolato L, Montemurro F et al (2014) Polyphenols from olive mill waste affect biofilm formation and motility in Escherichia coliK-12. Microb Biotechnol 7:265–275. doi:10.1111/1751-7915.12119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Casas-Sanchez J, Alsina AM, Herrlein MK, Mestres C (2007) Interaction between the antibacterial compound, oleuropein, and model membranes. Colloid Polym Sci 285:1351–1360. doi:10.1007/s00396-007-1693-x

    Article  CAS  Google Scholar 

  9. Caturla N, Pérez-Fons L, Estepa A, Micol V (2005) Differential effects of oleuropein, a biophenol from Olea europaea, on anionic and zwiterionic phospholipid model membranes. Chem Phys Lipids 137:2–17. doi:10.1016/j.chemphyslip.2005.04.003

    Article  CAS  PubMed  Google Scholar 

  10. Dey PM, Harborne JB (1997) Plant biochemistry. Academic press, San Diego, California

    Google Scholar 

  11. Dominciano LCC, Lee SHI, Corassin CH et al (2016) Effects of oleuropein and peracetic acid as sanitizing agents for inactivation of biofilms. Open Conf Proc J 7:1–6. doi:10.2174/2210289201607010001

    Article  CAS  Google Scholar 

  12. Durlu-özkaya F, Özkaya MT (2011) Oleuropein using as an additive for feed and products used for humans. Food Process Technol 2:1–7. doi:10.4172/2157-7110.1000113

    Google Scholar 

  13. Fleming HP, Walter WM Jr, Etchells JL (1973) Antimicrobial properties of oleuropein and products of its hydrolysis from green olives. Appl Microbiol 26:777–782

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Giamarellos-Bourboulis EJ, Geladopoulos T, Chrisofos M et al (2006) Oleuropein: a novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa. Shock 26:410–416. doi:10.1097/01.shk.0000226342.70904.06

    Article  CAS  PubMed  Google Scholar 

  15. Grandoni JA, Marta PT, Schloss JV (1998) Inhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents. J Antimicrob Chemother 42(4):475–482. doi:10.1093/jac/42.4.475

    Article  CAS  PubMed  Google Scholar 

  16. Gutiérrez-Correa J (2010) Trypanosoma cruzi dihydrolipoamide dehydrogenase as target of reactive metabolites generated by cytochrome c/hydrogen peroxide (or linoleic acid hydroperoxide)/phenol systems. Free Radic Res 44:1345–1358. doi:10.3109/10715762.2010.507669

    Article  CAS  PubMed  Google Scholar 

  17. Heinemann M, Kümmel A, Ruinatscha R, Panke S (2005) In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network. Biotechnol Bioeng 92:850–864. doi:10.1002/bit.20663

    Article  CAS  PubMed  Google Scholar 

  18. Janakat S, Al-Nabulsi AAR, Allehdan S et al (2015) Antimicrobial activity of amurca (olive oil lees) extract against selected foodborne pathogens. Food Sci Technol 35:259–265. doi:10.1590/1678-457X.6508

    Google Scholar 

  19. Juven B, Henis Y, Jacoby B (1972) Studies on the mechanism of the antimicrobial action of oleuropein*. J Appl Bacteriol 35:559–567. doi:10.1111/j.1365-2672.1972.tb03737.x

    Article  CAS  PubMed  Google Scholar 

  20. Lee DS, Burd H, Liu J et al (2009) Comparative genome-scale metabolic reconstruction and flux balance analysis of multiple Staphylococcus aureus genomes identify novel antimicrobial drug targets. J Bacteriol 191:4015–4024. doi:10.1128/JB.01743-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee SJ, Lee JH, Yang X et al (2015) Phenolic compounds: strong inhibitors derived from lignocellulosic hydrolysate for 2,3-butanediol production by Enterobacter aerogenes. Biotechnol J 10:1920–1928. doi:10.1002/biot.201500090

    Article  CAS  PubMed  Google Scholar 

  22. MacMillan SV, Alexander DA, Culham DE et al (1999) The ion coupling and organic substrate specificities of osmoregulatory transporter ProP in Escherichia coli. Biochim Biophys Acta Biomembr 1420:30–44. doi:10.1016/S0005-2736(99)00085-1

    Article  CAS  Google Scholar 

  23. Monk JM, Charusanti P, Aziz RK et al (2013) Genome-scale metabolic reconstructions of multiple Escherichia coli strains highlight strain-specific adaptations to nutritional environments. Proc Natl Acad Sci 110:20338–20343. doi:10.1073/pnas.1307797110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Oyedotun KS, Lemire BD (2004) The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase: homology modeling, cofactor docking, and molecular dynamics simulation studies. J Biol Chem 279:9424–9431. doi:10.1074/jbc.M311876200

    Article  CAS  PubMed  Google Scholar 

  25. Patel S, Cichello S (2013) Manuka honey: an emerging natural food with medicinal use. Nat Prod Bioprospect 3:121–128. doi:10.1007/s13659-013-0018-7

    Article  CAS  PubMed Central  Google Scholar 

  26. Pereira AP, Ferreira ICFR, Marcelino F et al (2007) Phenolic compounds and antimicrobial activity of olive (Olea europaea L. Cv. Cobrançosa) leaves. Molecules 12:1153–1162. doi:10.3390/12051153

    Article  CAS  PubMed  Google Scholar 

  27. Perpetuini G, Scornec H, Tofalo R et al (2013) Identification of critical genes for growth in olive brine by transposon mutagenesis of lactobacillus pentosus C11. Appl Environ Microbiol 79:4568–4575. doi:10.1128/AEM.01159-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ramawat KG (2013) Biological activity of oleuropein and its derivatives. Nat Prod. doi:10.1038/188440b0

    Article  Google Scholar 

  29. Rivas-Sendra A, Landete JM, Alcántara C, Zúñiga M (2011) Response of Lactobacillus casei BL23 to phenolic compounds. J Appl Microbiol 111:1473–1481. doi:10.1111/j.1365-2672.2011.05160.x

    Article  CAS  PubMed  Google Scholar 

  30. Romantsov T, Stalker L, Culham DE, Wood JM (2008) Cardiolipin controls the osmotic stress response and the subcellular location of transporter ProP in Escherichia coli. J Biol Chem 283:12314–12323. doi:10.1074/jbc.M709871200

    Article  CAS  PubMed  Google Scholar 

  31. Seborg DE, Mellichamp DA, Edgar TF, Doyle FJ III (2010) Process dynamics and control. Wiley, Hoboken, NJ

    Google Scholar 

  32. Smith DM, Dou QP (2001) Green tea polyphenol epigallocatechin inhibits DNA replication and consequently induces leukemia cell apoptosis. Int J Mol Med 7:645–652

    CAS  PubMed  Google Scholar 

  33. Talhaoui N, Vezza T, Gómez-Caravaca AM et al (2016) Phenolic compounds and in vitro immunomodulatory properties of three Andalusian olive leaf extracts. J Funct Foods 22:270–277. doi:10.1016/j.jff.2016.01.037

    Article  CAS  Google Scholar 

  34. Tassou CC, Nychas GJE (1994) Inhibition of Staphylococcus aureus by Olive Phenolics in broth and in a model food system. J Food Prot 57:5

    Google Scholar 

  35. Tranter HS, Tassou SC, Nychas GJ (1993) The effect of the olive phenolic compound, oleuropein, on growth and enterotoxin B production by Staphylococcus aureus. J Appl Bacteriol 74:253–259. doi:10.1111/j.1365-2672.1993.tb03023.x

    Article  CAS  PubMed  Google Scholar 

  36. Tuck KL, Tuck KL, Hayball PJ (2002) Major phenolic compounds in olive oil: metabolism and health effects. J Nutr Biochem major phenolic compounds in olive oil: metabolism and health effects 2863:636–644. doi:10.1016/S0955-2863(02)00229-2

    Google Scholar 

  37. Votyakova T, Bottino R, Trucco M (2012) Mitochondria and antioxidants: the active players in islet oxidative stress. In: Ekinci D (ed) Chemical Biology. InTech, Rijeka, Croatia

    Google Scholar 

  38. Watanabe Y, Kamei A, Shinozaki F et al (2011) Ingested maple syrup evokes a possible liver-protecting effect—physiologic and genomic investigations with rats. Biosci Biotechnol Biochem 75:2408–2410. doi:10.1271/bbb.110532

    Article  CAS  PubMed  Google Scholar 

  39. Wenzel M, Patra M et al (2011) Proteomic signature of fatty acid biosynthesis inhibition available for in vivo mechanism-of-action studies. Antimicrob Agents Chemother 55(6):2590–2596. doi:10.1128/AAC.00078-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Widiastuti H, Kim JY, Selvarasu S et al (2011) Genome-scale modeling and in silico analysis of ethanologenic bacteria Zymomonas mobilis. Biotechnol Bioeng 108:655–665

    Article  CAS  PubMed  Google Scholar 

  41. Xu Z, Fang X, Wood TK, Huang ZJ (2013) A systems-level approach for investigating pseudomonas aeruginosa biofilm formation. PLoS One 8:1–14

    Google Scholar 

  42. Xu Z, Islam S, Wood TK, Huang Z (2015) An integrated modeling and experimental approach to study the influence of environmental nutrients on biofilm formation of Pseudomonas aeruginosa. Biomed Res Int 2015:1–12. doi:10.1155/2015/506782

    CAS  Google Scholar 

  43. Zhang C, Ji B, Mardinoglu A, Nielsen J, Hua Q (2015) Logical transformation of genome-scale metabolic models for gene level applications and analysis. Bioinformatics btv134. doi:10.1093/bioinformatics/btv134

    Google Scholar 

Download references

Acknowledgments

Funding was provided by Villanova VCASE Seed Grant.

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, Villanova University, Villanova, PA, USA

    Xianhua Li, Virginia LaMacchia, Kathryn O’Donoghue & Zuyi Huang

  2. Molecular Characterization of Foodborne Pathogens, Eastern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, 600 East Mermaid Lane, Wyndmoor, PA, 19038, USA

    Yanhong Liu

  3. Department of Health and Exercise Science, Rowan University, Glassboro, NJ, USA

    Qian Jia

Authors
  1. Xianhua Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanhong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qian Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Virginia LaMacchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathryn O’Donoghue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zuyi Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zuyi Huang.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Liu, Y., Jia, Q. et al. A systems biology approach to investigate the antimicrobial activity of oleuropein. J Ind Microbiol Biotechnol 43, 1705–1717 (2016). https://doi.org/10.1007/s10295-016-1841-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-016-1841-8

Keywords

Search

Navigation