Skip to main content
SpringerLink
Log in

Propionate, together with triple antibiotics, inhibits the growth of Enterococci

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Enterococci are Gram-positive facultative anaerobic bacteria that colonize the oral cavity and gastrointestinal tract. Enterococcal infections, mainly caused by Enterococcus faecalis and Enterococcus faecium, include apical periodontitis, endocarditis, and bloodstream infections. Recently, vancomycinresistant Enterococci are considered major pathogens that are common but difficult to treat, especially in nosocomial settings. Moreover, E. faecalis is closely associated with recurrent endodontic infections and failed endodontic treatment. In this study, we investigated the effects of short-chain fatty acids (SCFAs), acetate, propionate, and butyrate, which are metabolites fermented by gut microbiota, on the growth of Enterococci. Enterococci were cultured in the presence or absence of acetate, propionate, or butyrate, and the optical density at 600 nm was measured to determine bacterial growth. The minimum inhibitory concentration/minimum bactericidal concentration test was conducted. Bacteria were treated with a SCFA, together with clinically used endodontic treatment methods such as triple antibiotics (metronidazole, minocycline, and ciprofloxacin) and chlorhexidine gluconate (CHX) to determine the effects of combination treatment. Of the SCFAs, propionate had a bacteriostatic effect, inhibiting the growth of E. faecalis in a dose-dependent manner and also that of clinical strains of E. faecalis isolated from dental plaques. Meanwhile, acetate and butyrate had minimal effects on E. faecalis growth. Moreover, propionate inhibited the growth of other Enterococci including E. faecium. In addition, combination treatment of propionate and triple antibiotics led to further growth inhibition, whereas no cooperative effect was observed at propionate plus CHX. These results indicate that propionate attenuates the growth of Enterococci, suggesting propionate as a potential agent to control Enterococcal infections, especially when combined with triple antibiotics.

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

Similar content being viewed by others

References

  • Arias, C.A. and Murray, B.E. 2012. The rise of the Enterococcus: Beyond vancomycin resistance. Nat. Rev. Microbiol. 10, 266–278.

    Article  CAS  Google Scholar 

  • Babich, H., Wurzburger, B.J., Rubin, Y.L., Sinensky, M.C., and Blau, L. 1995. An in vitro study on the cytotoxicity of chlorhexidine digluconate to human gingival cells. Cell. Biol. Toxicol. 11, 79–88.

    Article  CAS  Google Scholar 

  • Brock, M. and Buckel, W. 2004. On the mechanism of action of the antifungal agent propionate. Eur. J. Biochem. 271, 3227–3241.

    Article  CAS  Google Scholar 

  • Cetinkaya, Y., Falk, P., and Mayhall, C.G. 2000. Vancomycin-resistant Enterococci. Clin. Microbiol. Rev. 13, 686–707.

    Article  CAS  Google Scholar 

  • CLSI. 2012. Tests for bacteria that grow aerobically; approved standard — ninth edition. CLSI Document M07-A9. CLSI, Wayne, PA, USA.

    Google Scholar 

  • Cummings, J.H., Pomare, E.W., Branch, W.J., Naylor, C.P., and Macfarlane, G.T. 1987. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221–1227.

    Article  CAS  Google Scholar 

  • Dolan, S.K., Wijaya, A., Geddis, S.M., Spring, D.R., Silva-Rocha, R., and Welch, M. 2018. Loving the poison: The methylcitrate cycle and bacterial pathogenesis. Microbiology 164, 251–259.

    Article  CAS  Google Scholar 

  • Evans, M., Davies, J.K., Sundqvist, G., and Figdor, D. 2002. Mechanisms involved in the resistance of Enterococcus faecalis to calcium hydroxide. Int. Endod. J. 35, 221–228.

    Article  CAS  Google Scholar 

  • Gentry-Weeks, C.R., Karkhoff-Schweizer, R., Pikis, A., Estay, M., and Keith, J.M. 1999. Survival of Enterococcus faecalis in mouse peritoneal macrophages. Infect. Immun. 67, 2160–2165.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gu, Y.H., Yamasita, T., and Kang, K.M. 2018. Subchronic oral dose toxicity study of Enterococcus faecalis 2001 (ef 2001) in mice. Toxicol. Res. 34, 55–63.

    Article  CAS  Google Scholar 

  • Hancock, H.H. 3rd, Sigurdsson, A., Trope, M., and Moiseiwitsch, J. 2001. Bacteria isolated after unsuccessful endodontic treatment in a North American population. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 91, 579–586.

    Article  Google Scholar 

  • Hebert, L., Courtin, P., Torelli, R., Sanguinetti, M., Chapot-Chartier, M.P., Auffray, Y., and Benachour, A. 2007. Enterococcus faecalis constitutes an unusual bacterial model in lysozyme resistance. Infect. Immun. 75, 5390–5398.

    Article  CAS  Google Scholar 

  • Jacobson, A., Lam, L., Rajendram, M., Tamburini, F., Honeycutt, J., Pham, T., Van Treuren, W., Pruss, K., Stabler, S.R., Lugo, K., et al. 2018. A gut commensal-produced metabolite mediates colonization resistance to salmonella infection. Cell Host Microbe 24, 296–307. e7.

    Article  CAS  Google Scholar 

  • Jeong, S., Kim, H.Y., Kim, A.R., Yun, C.H., and Han, S.H. 2019. Propionate ameliorates Staphylococcus aureus skin infection by attenuating bacterial growth. Front. Microbiol. 10, 1363.

    Article  Google Scholar 

  • Kim, J.H., Kim, Y., Shin, S.J., Park, J.W., and Jung, I.Y. 2010. Tooth discoloration of immature permanent incisor associated with triple antibiotic therapy: A case report. J. Endod. 36, 1086–1091.

    Article  Google Scholar 

  • Kirchhoff, A.L., Raldi, D.P., Salles, A.C., Cunha, R.S., and Mello, I. 2015. Tooth discolouration and internal bleaching after the use of triple antibiotic paste. Int. Endod. J. 48, 1181–1187.

    Article  CAS  Google Scholar 

  • Koh, A., De Vadder, F., Kovatcheva-Datchary, P., and Backhed, F. 2016. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell 165, 1332–1345.

    Article  CAS  Google Scholar 

  • Lin, Y.H., Mickel, A.K., and Chogle, S. 2003. Effectiveness of selected materials against Enterococcus faecalis: Part 3. The antibacterial effect of calcium hydroxide and chlorhexidine on Enterococcus faecalis. J. Endod. 29, 565–566.

    Article  Google Scholar 

  • Lobritz, M.A., Belenky, P., Porter, C.B., Gutierrez, A., Yang, J.H., Schwarz, E.G., Dwyer, D.J., Khalil, A.S., and Collins, J.J. 2015. Antibiotic efficacy is linked to bacterial cellular respiration. Proc. Natl. Acad. Sci. USA 112, 8173–8180.

    Article  CAS  Google Scholar 

  • Maruyama, K. and Kitamura, H. 1985. Mechanisms of growth inhibition by propionate and restoration of the growth by sodium bicarbonate or acetate in Rhodopseudomonas sphaeroides. J. Biochem. 98, 819–824.

    Article  CAS  Google Scholar 

  • McHugh, C.P., Zhang, P., Michalek, S., and Eleazer, P.D. 2004. pH required to kill Enterococcus faecalis in vitro. J. Endod. 30, 218–219.

    Article  Google Scholar 

  • Miller, W.R., Munita, J.M., and Arias, C.A. 2014. Mechanisms of antibiotic resistance in enterococci. Expert. Rev. Anti. Infect. Ther. 12, 1221–1236.

    Article  CAS  Google Scholar 

  • Mohammadi, Z. 2008. Chlorhexidine gluconate, its properties and applications in endodontics. Iran Endod. J. 2, 113–125.

    PubMed  PubMed Central  Google Scholar 

  • Pemberton, M.N. 2016. Allergy to chlorhexidine. Dent. Update 43, 272–274.

    Article  Google Scholar 

  • Rakita, R.M., Vanek, N.N., Jacques-Palaz, K., Mee, M., Mariscalco, M.M., Dunny, G.M., Snuggs, M., Van Winkle, W.B., and Simon, S.I. 1999. Enterococcus faecalis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation. Infect. Immun. 67, 6067–6075.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rocco, C.J. and Escalante-Semerena, J.C. 2010. In Salmonella enterica, 2-methylcitrate blocks gluconeogenesis. J. Bacteriol. 192, 771–778.

    Article  CAS  Google Scholar 

  • Roe, A.J., O’Byrne, C., McLaggan, D., and Booth, I.R. 2002. Inhibition of Escherichia coli growth by acetic acid: A problem with methionine biosynthesis and homocysteine toxicity. Microbiology 148, 2215–2222.

    Article  CAS  Google Scholar 

  • Siqueira, J.F. Jr. and Rocas, I.N. 2004. Polymerase chain reaction-based analysis of microorganisms associated with failed endodontic treatment. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 97, 85–94.

    Article  Google Scholar 

  • Stuart, C.H., Schwartz, S.A., Beeson, T.J., and Owatz, C.B. 2006. Enterococcus faecalis: Its role in root canal treatment failure and current concepts in retreatment. J. Endod. 32, 93–98.

    Article  Google Scholar 

  • Tendolkar, P.M., Baghdayan, A.S., and Shankar, N. 2003. Pathogenic Enterococci: New developments in the 21st century. Cell. Mol. Life Sci. 60, 2622–2636.

    Article  CAS  Google Scholar 

  • Vijayaraghavan, R., Mathian, V.M., Sundaram, A.M., Karunakaran, R., and Vinodh, S. 2012. Triple antibiotic paste in root canal therapy. J. Pharm. Bioallied Sci. 4, S230–233.

    Article  Google Scholar 

  • Yonezawa, H., Osaki, T., Hanawa, T., Kurata, S., Zaman, C., Woo, T.D., Takahashi, M., Matsubara, S., Kawakami, H., Ochiai, K., et al. 2012. Destructive effects of butyrate on the cell envelope of Helicobacter pylori. J. Med. Microbiol. 61, 582–589.

    Article  CAS  Google Scholar 

  • Zimmermann, G.R., Lehar, J., and Keith, C.T. 2007. Multi-target therapeutics: When the whole is greater than the sum of the parts. Drug Discov. Today 12, 34–42.

    Article  CAS  Google Scholar 

  • Zorko, M. and Jerala, R. 2008. Alexidine and chlorhexidine bind to lipopolysaccharide and lipoteichoic acid and prevent cell activation by antibiotics. J. Antimicrob. Chemother. 62, 730–737.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Korean Collection for Oral Microbiology and Korean Agricultural Culture Collection for kindly providing Enterococcal strains. This work was supported by grants from the National Research Foundation of Korea, which is funded by the Korean government (NRF-2019R1A2C2007041 and NRF-2018R1A5A2024418) and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (HI17C1377), Republic of Korea.

Author information

Authors and Affiliations

  1. Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, 08826, Republic of Korea

    Soyoung Jeong, Yunjae Lee, Ok-Jin Park & Seung Hyun Han

  2. College of Liberal Studies, Seoul National University, Seoul, 08826, Republic of Korea

    Yunjae Lee

  3. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea

    Cheol-Heui Yun

  4. Institutes of Green Bio Science and Technology, Seoul National University, Pyeongchang, 25354, Republic of Korea

    Cheol-Heui Yun

Authors
  1. Soyoung Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yunjae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheol-Heui Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ok-Jin Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seung Hyun Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ok-Jin Park or Seung Hyun Han.

Ethics declarations

The authors deny any conflicts of interest related to this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jeong, S., Lee, Y., Yun, CH. et al. Propionate, together with triple antibiotics, inhibits the growth of Enterococci. J Microbiol. 57, 1019–1024 (2019). https://doi.org/10.1007/s12275-019-9434-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-019-9434-7

Keywords

Search

Navigation