Advertisement

Polyphenols as resistance modulators in Arcobacter butzleri

  • Vanessa Sousa
  • Ângelo Luís
  • Mónica Oleastro
  • Fernanda Domingues
  • Susana Ferreira
Original Article
  • 13 Downloads

Abstract

Arcobacter butzleri is an emerging human and animal pathogen for which an increased prevalence of resistance to antibiotics has been observed, and so alternative compounds to modulate resistance of A. butzleri are required. This work aims to study the potential use of several polyphenols as efflux pump inhibitors (EPIs) and to evaluate their interaction with antibiotics, in order to enhance antibiotic activity against A. butzleri. The minimum inhibitory concentration (MIC) of (−)-epicatechin, (+)-catechin, rutin, gallic acid, caffeic acid, chlorogenic acid, resveratrol, pterostilbene, and pinosylvin was determined, in absence and presence of four known EPIs. Subsequently, ethidium bromide accumulation in presence of subinhibitory concentrations of polyphenols was evaluated, and the synergistic potential of the compounds with antibiotics was assessed by checkerboard dilution test. Only stilbenes presented activity against A. butzleri, with MIC values ranging between 64 and 512 μg/mL. The MIC determination of the polyphenols in the presence of subinhibitory concentrations of known EPIs showed that efflux pumps play a role in the resistance to these compounds. Stilbenes also induced a higher intracellular accumulation of ethidium bromide, indicating that they may inhibit the activity of efflux pumps. Checkerboard assays showed that several combinations of polyphenol/antibiotic had an additive effect against A. butzleri. Overall, the results indicate that some polyphenols reduce A. butzleri resistance to antibiotics, suggesting the potential of stilbenes as EPIs. The potential of resveratrol and pinosylvin as resistance modulators was evidenced, insofar as these compounds can even revert antibiotic resistance. Therefore, the use of polyphenols as resistance modulators could be an alternative to overcome the decreasing susceptibility of A. butzleri to antibiotics.

Notes

Funding information

Susana Ferreira was supported by a fellowship (SFRH/BPD/101959/2014) from Fundação para a Ciência e Tecnologia and co-financed by Fundo Social Europeu. This work was supported by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I—Strengthening research, technological development, and innovation (Project POCI-01-0145-FEDER-007491) and National Funds by FCT - Foundation for Science and Technology (Project UID/Multi/00709/2013).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Alakomi H, Puupponen-pimiä R, Aura A, Helander IM (2007) Weakening of Salmonella with selected microbial metabolites of berry-derived phenolic compounds and organic acids. J Agric Food Chem 55:3905–3912CrossRefGoogle Scholar
  2. Collado L, Figuera MJ (2011) Taxonomy, epidemiology, and clinical relevance of the genus Arcobacter. Clin Microbiol Rev 24:174–192CrossRefGoogle Scholar
  3. Duarte A, Alves AC, Ferreira S, Silva F, Domingues FC (2015) Resveratrol inclusion complexes: antibacterial and anti-biofilm activity against Campylobacter spp. and Arcobacter butzleri. Food Res Int 77:244–250CrossRefGoogle Scholar
  4. Ferreira S, Fraqueza MJ, Queiroz JA, Domingues FC, Oleastro M (2013) Genetic diversity, antibiotic resistance and biofilm-forming ability of Arcobacter butzleri isolated from poultry and environment from a Portuguese slaughterhouse. Int J Food Microbiol 162:82–88CrossRefGoogle Scholar
  5. Ferreira S, Silva F, Queiroz JA, Oleastro M, Domingues FC (2014) Resveratrol against Arcobacter butzleri and Arcobacter cryaerophilus: activity and effect on cellular functions. Int J Food Microbiol 180:62–68CrossRefGoogle Scholar
  6. Ferreira S, Oleastro M, Domingues F (2017a) Arcobacter spp. in food chain - from culture to omics. In: Singh OV (ed) Food borne pathogens and antibiotic resistance. Wiley-Blackwell, New Jersey, pp 73–118CrossRefGoogle Scholar
  7. Ferreira S, Oleastro M, Domingues FC (2017b) Occurrence, genetic diversity and antibiotic resistance of Arcobacter sp. in a dairy plant. J Appl Microbiol 123:1019–1026CrossRefGoogle Scholar
  8. Ferreira S, Correia DR, Oleastro M, Domingues FC (2018) Arcobacter butzleri ciprofloxacin resistance: point mutations in DNA gyrase a and role on fitness cost. Microb Drug Resist 24:915–922CrossRefGoogle Scholar
  9. International Commission on Microbiological Specifications for Foods (ICMSF) (2002) Microorganisms in food 7—microbiological testing in food safety management. Kluwer Academic/Plenum Publishers, New YorkCrossRefGoogle Scholar
  10. Jung CM, Heinze TM, Schnackenberg LK, Mullis LB, Elkins SA, Elkins CA, Steele RS, Sutherland JB (2009) Interaction of dietary resveratrol with animal-associated bacteria. FEMS Microbiol Lett 297:266–273CrossRefGoogle Scholar
  11. Klančnik A, Možina SS, Zhang Q (2012) Anti-Campylobacter activities and resistance mechanisms of natural phenolic compounds in Campylobacter. PLoS One 7:e51800CrossRefGoogle Scholar
  12. Klančnik A, Pogačar MS, Trošt K, Žnidarič MT, Vodopivec BM, Možina SS (2016) Anti-Campylobacter activity of resveratrol and an extract from waste pinot noir grape skins and seeds, and resistance of Campylobacter jejuni planktonic and biofilm cells, mediated via the CmeABC efflux pump. J Appl Microbiol 122:65–77CrossRefGoogle Scholar
  13. Lee WX, Basri DF, Ghazali AR, Jeandet P (2017) Bactericidal effect of pterostilbene alone and in combination with gentamicin against human pathogenic bacteria. Molecules 22:E463CrossRefGoogle Scholar
  14. Lima VN, Oliveira-Tintino CDM, Santos ES, Morais LP, Tintino SR, Freitas TS, Geraldo YS, Pereira RLS, Cruz RP, Menezes IRA, Coutinho HDM (2016) Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol. Microb Pathog 99:56–61CrossRefGoogle Scholar
  15. Lomovskaya O, Warren MS, Lee A, Fronko R, Lee M, Blais J, Chamberland S, Renau T, Leger R, Hecker S, Watkins W, Hoshino K, Ishida H, Lee VJ, Galazzo J, Lee MY, Cho D, Renau TOM (2001) Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob Agents Chemother 45:105–116CrossRefGoogle Scholar
  16. Miller WG, Parker CT, Rubenfield M, Mendz GL, Wösten MMSM, Ussery DW, Stolz JF, Binnewies TT, Hallin PF, Wang G, Malek JA, Rogosin A, Stanker LH, Mandrell RE (2007) The complete genome sequence and analysis of the epsilonproteobacterium Arcobacter butzleri. PLoS One 2:e1358CrossRefGoogle Scholar
  17. Oh E, Jeon B (2015) Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds. Front Microbiol 6:1129Google Scholar
  18. Pastorkova E, Zakova T, Landa P, Novakova J, Vadlejch J, Kokoska L (2013) Growth inhibitory effect of grape phenolics against wine spoilage yeasts and acetic acid bacteria. Int J Food Microbiol 161:209–213CrossRefGoogle Scholar
  19. Paulo L, Ferreira S, Gallardo E, Queiroz JA, Domingues F (2010) Antimicrobial activity and effects of resveratrol on human pathogenic bacteria. World J Microbiol Biotechnol 26:1533–1538CrossRefGoogle Scholar
  20. Plumed-Ferrer C, Vakevainen K, Komulainen H, Rautiainen M, Smeds A, Raitanen JE, Eklund P, Willfor S, Alakomi HL, Saarela M, Von Wright A (2013) The antimicrobial effects of wood-associated polyphenols on food pathogens and spoilage organisms. Int J Food Microbiol 164:99–107CrossRefGoogle Scholar
  21. Sanhueza L, Melo R, Montero R, Maisey K, Mendoza L, Wilkens M (2017) Synergistic interactions between phenolic compounds identified in grape pomace extract with antibiotics of different classes against Staphylococcus aureus and Escherichia coli. PLoS One 12:e0172273CrossRefGoogle Scholar
  22. Silva F, Nerín C, Domingues FC (2015) Stilbene phytoallexins inclusion complexes: a natural-based strategy to control foodborne pathogen Campylobacter. Food Control 54:66–73CrossRefGoogle Scholar
  23. Simões M, Bennett RN, Rosa EA (2009) Understanding antimicrobial activities of phytochemicals against multidrug resistant bacteria and biofilms. Nat Prod Rep 26:746–757Google Scholar
  24. Son I, Englen MD, Berrang M, Fedorka-Cray PJ, Harrison MA (2007) Antimicrobial resistance of Arcobacter and Campylobacter from broiler carcasses. Int J Antimicrob Agents 29:451–455CrossRefGoogle Scholar
  25. Sopirala MM, Mangino JE, Gebreyes WA, Biller B, Bannerman T, Balada-Llasat JM, Pancholi P (2010) Synergy testing by Etest, microdilution checkerboard, and time-kill methods for pan-drug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 54:4678–4683CrossRefGoogle Scholar
  26. Stavri M, Piddock LJV, Gibbons S (2007) Bacterial efflux pump inhibitors from natural sources. J Antimicrob Chemother 59:1247–1260CrossRefGoogle Scholar
  27. Van den Abeele A-M, Vogelaers D, Vanlaere E, Houf K (2016) Antimicrobial susceptibility testing of Arcobacter butzleri and Arcobacter cryaerophilus strains isolated from Belgian patients. J Antimicrob Chemother 71:1241–1244CrossRefGoogle Scholar
  28. Venter H, Mowla R, Ohene-Agyei T, Ma S (2015) RND-type drug efflux pumps from gram-negative bacteria: molecular mechanism and inhibition. Front Microbiol 6:377CrossRefGoogle Scholar
  29. Vicente-Martins S, Oleastro M, Domingues FC, Ferreira S (2018) Arcobacter spp. at retail food from Portugal: prevalence, genotyping and antibiotics resistance. Food Control 85:107–112CrossRefGoogle Scholar
  30. Webber MA, Piddock LJV (2003) The importance of efflux pumps in bacterial antibiotic resistance. J Antimicrob Chemother 51:9–11CrossRefGoogle Scholar
  31. Zacchino SA, Butassi E, DiLiberto M, Raimondi M, Postigo A, Sortino M (2017) Plant phenolics and terpenoids as adjuvants of antibacterial and antifungal drugs. Phytomedicine 37:27–48CrossRefGoogle Scholar

Copyright information

© Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2019

Authors and Affiliations

  1. 1.CICS-UBI-Centro de Investigação em Ciências da SaúdeUniversidade da Beira InteriorCovilhãPortugal
  2. 2.Department of Infectious Diseases, National Reference Laboratory for Gastrointestinal InfectionsNational Institute of Health Dr. Ricardo JorgeLisbonPortugal

Personalised recommendations