The Increasing Issue of Vancomycin-Resistant Enterococci and the Bacteriocin Solution

  • Ingvild S. Reinseth
  • Kirill V. Ovchinnikov
  • Hanne H. Tønnesen
  • Harald Carlsen
  • Dzung B. DiepEmail author


Enterococci are commensals of human and other animals’ gastrointestinal tracts. Only making up a small part of the microbiota, they have not played a significant role in research, until the 1980s. Although the exact year is variable according to different geographical areas, this was the decade when vancomycin-resistant enterococci (VRE) were discovered and since then their role as causative agents of human infections has increased. Enterococcus faecium is on the WHO’s list of “bacteria for which new antibiotics are urgently needed,” and with no new antibiotics in development, the situation is desperate. In this review, different aspects of VRE are outlined, including the mortality caused by VRE, antibiotic resistance profiles, animal-modeling efforts, and virulence. In addition, the limitations of current antibiotic treatments for VRE and prospective new treatments, such as bacteriocins, are reviewed.


Enterococcus faecium Enterococcus faecalis VRE Antibiotic resistance Virulence Bacteriocin 


Funding Information

This work was supported by grants from the Research Council of Norway (project numbers 275190 and 273646) and from the Bio-based Industries Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 790507.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Aarestrup FM, Agerso Y, Gerner-Smidt P, Madsen M, Jensen LB (2000) Comparison of antimicrobial resistance phenotypes and resistance genes in Enterococcus faecalis and Enterococcus faecium from humans in the community, broilers, and pigs in Denmark. Diagn Microbiol Infect Dis 37(2):127–137CrossRefGoogle Scholar
  2. 2.
    Abele-Horn M, Vogel U, Klare I, Konstabel C, Trabold R, Kurihara R, Witte W, Kreth W, Schlegel PG, Claus H (2006) Molecular epidemiology of hospital-acquired vancomycin-resistant enterococci. J Clin Microbiol 44(11):4009–4013. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Adams DJ, Eberly MD, Goudie A, Nylund CM (2016) Rising vancomycin-resistant Enterococcus infections in hospitalized children in the United States. Hosp Pediatr 6(7):404–411. CrossRefPubMedGoogle Scholar
  4. 4.
    Akhtar N, Sultan F, Nizamuddin S, Zafar W (2016) Risk factors and clinical outcomes for vancomycin-resistant Enterococcus bacteraemia in hospitalised cancer patients in Pakistan: a case-control study. J Pak Med Assoc 66(7):829–836PubMedGoogle Scholar
  5. 5.
    Akiyama Y, Kanehara K, Ito K (2004) RseP (YaeL), an Escherichia coli RIP protease, cleaves transmembrane sequences. EMBO J 23(22):4434–4442. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ankaiah D, Palanichamy E, Antonyraj CB, Ayyanna R, Perumal V, Ahamed SIB, Arul V (2018) Cloning, overexpression, purification of bacteriocin enterocin-B and structural analysis, interaction determination of enterocin-a, B against pathogenic bacteria and human cancer cells. Int J Biol Macromol 116:502–512. CrossRefPubMedGoogle Scholar
  7. 7.
    Arias CA, Contreras GA, Murray BE (2010) Management of multidrug-resistant enterococcal infections. Clin Microbiol Infect 16(6):555–562. CrossRefPubMedGoogle Scholar
  8. 8.
    Arias CA, Murray BE (2012) The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 10(4):266–278. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Arias CA, Panesso D, McGrath DM, Qin X, Mojica MF, Miller C, Diaz L, Tran TT, Rincon S, Barbu EM, Reyes J, Roh JH, Lobos E, Sodergren E, Pasqualini R, Arap W, Quinn JP, Shamoo Y, Murray BE, Weinstock GM (2011) Genetic basis for in vivo daptomycin resistance in enterococci. N Engl J Med 365(10):892–900. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Brade KD, Rybak JM, Rybak MJ (2016) Oritavancin: a new lipoglycopeptide antibiotic in the treatment of Gram-positive infections. Infect Dis Ther 5(1):1–15. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Brand AM, de Kwaadsteniet M, Dicks LM (2010) The ability of nisin F to control Staphylococcus aureus infection in the peritoneal cavity, as studied in mice. Lett Appl Microbiol 51(6):645–649. CrossRefPubMedGoogle Scholar
  12. 12.
    Brandl K, Plitas G, Mihu CN, Ubeda C, Jia T, Fleisher M, Schnabl B, DeMatteo RP, Pamer EG (2008) Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455(7214):804–807. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Brandl K, Plitas G, Schnabl B, DeMatteo RP, Pamer EG (2007) MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med 204(8):1891–1900. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Brown MS, Ye J, Rawson RB, Goldstein JL (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100(4):391–398CrossRefGoogle Scholar
  15. 15.
    Buffie CG, Pamer EG (2013) Microbiota-mediated colonization resistance against intestinal pathogens. Nat Rev Immunol 13(11):790–801. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Caballero S, Carter R, Ke X, Susac B, Leiner IM, Kim GJ, Miller L, Ling L, Manova K, Pamer EG (2015) Distinct but spatially overlapping intestinal niches for vancomycin-resistant Enterococcus faecium and carbapenem-resistant Klebsiella pneumoniae. PLoS Pathog 11(9):e1005132. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Caly DL, Chevalier M, Flahaut C, Cudennec B, Al Atya AK, Chataigne G, D'Inca R, Auclair E, Drider D (2017) The safe enterocin DD14 is a leaderless two-peptide bacteriocin with anti-Clostridium perfringens activity. Int J Antimicrob Agents 49(3):282–289. CrossRefPubMedGoogle Scholar
  18. 18.
    Casapao AM, Kullar R, Davis SL, Levine DP, Zhao JJ, Potoski BA, Goff DA, Crank CW, Segreti J, Sakoulas G, Cosgrove SE, Rybak MJ (2013) Multicenter study of high-dose daptomycin for treatment of enterococcal infections. Antimicrob Agents Chemother 57(9):4190–4196. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Cebrián R, Rodríguez-Cabezas ME, Martín-Escolano R, Rubiño S, Garrido-Barros M, Montalbán-López M, Rosales MJ, Sánchez-Moreno M, Valdivia E, Martínez-Bueno M, Marín C, Galvez J, Maqueda M (2019) Preclinical studies of toxicity and safety of the AS-48 bacteriocin. J Adv Res. CrossRefGoogle Scholar
  20. 20.
    Chi H, Holo H (2018) Synergistic antimicrobial activity between the broad spectrum bacteriocin garvicin KS and nisin, farnesol and polymyxin B against Gram-positive and Gram-negative bacteria. Curr Microbiol 75(3):272–277. CrossRefPubMedGoogle Scholar
  21. 21.
    Chuang YC, Wang JT, Lin HY, Chang SC (2014) Daptomycin versus linezolid for treatment of vancomycin-resistant enterococcal bacteremia: systematic review and meta-analysis. BMC Infect Dis 14:687. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Cintas LM, Casaus P, Havarstein LS, Hernandez PE, Nes IF (1997) Biochemical and genetic characterization of enterocin P, a novel sec-dependent bacteriocin from Enterococcus faecium P13 with a broad antimicrobial spectrum. Appl Environ Microbiol 63(11):4321–4330PubMedPubMedCentralGoogle Scholar
  23. 23.
    Comerlato CB, Resende MC, Caierao J, d'Azevedo PA (2013) Presence of virulence factors in Enterococcus faecalis and Enterococcus faecium susceptible and resistant to vancomycin. Mem Inst Oswaldo Cruz 108(5):590–595CrossRefGoogle Scholar
  24. 24.
    Cook LC, Federle MJ (2014) Peptide pheromone signaling in Streptococcus and Enterococcus. FEMS Microbiol Rev 38(3):473–492. CrossRefPubMedGoogle Scholar
  25. 25.
    Cotter PD (2014) An ‘Upp’-turn in bacteriocin receptor identification. Mol Microbiol 92(6):1159–1163. CrossRefPubMedGoogle Scholar
  26. 26.
    Cotter PD, Hill C, Ross RP (2005) Bacteriocins: developing innate immunity for food. Nat Rev Microbiol 3(10):777–788. CrossRefPubMedGoogle Scholar
  27. 27.
    Cotter PD, Ross RP, Hill C (2013) Bacteriocins—a viable alternative to antibiotics? Nat Rev Microbiol 11(2):95–105. CrossRefPubMedGoogle Scholar
  28. 28.
    Crank CW, Scheetz MH, Brielmaier B, Rose WE, Patel GP, Ritchie DJ, Segreti J (2010) Comparison of outcomes from daptomycin or linezolid treatment for vancomycin-resistant enterococcal bloodstream infection: a retrospective, multicenter, cohort study. Clin Ther 32(10):1713–1719. CrossRefPubMedGoogle Scholar
  29. 29.
    Crouzet L, Derrien M, Cherbuy C, Plancade S, Foulon M, Chalin B, van Hylckama Vlieg JET, Grompone G, Rigottier-Gois L, Serror P (2018) Lactobacillus paracasei CNCM I-3689 reduces vancomycin-resistant Enterococcus persistence and promotes Bacteroidetes resilience in the gut following antibiotic challenge. Sci Rep 8(1):5098. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Darwin AJ (2013) Stress relief during host infection: the phage shock protein response supports bacterial virulence in various ways. PLoS Pathog 9(7):e1003388. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Darwin AJ, Miller VL (1999) Identification of Yersinia enterocolitica genes affecting survival in an animal host using signature-tagged transposon mutagenesis. Mol Microbiol 32(1):51–62CrossRefGoogle Scholar
  32. 32.
    De Kwaadsteniet M, Doeschate KT, Dicks LM (2009) Nisin F in the treatment of respiratory tract infections caused by Staphylococcus aureus. Lett Appl Microbiol 48(1):65–70. CrossRefPubMedGoogle Scholar
  33. 33.
    de Kwaadsteniet M, van Reenen CA, Dicks LM (2010) Evaluation of nisin F in the treatment of subcutaneous skin infections, as monitored by using a bioluminescent strain of Staphylococcus aureus. Probiotics Antimicrob Proteins 2(2):61–65. CrossRefPubMedGoogle Scholar
  34. 34.
    Deshpande LM, Ashcraft DS, Kahn HP, Pankey G, Jones RN, Farrell DJ, Mendes RE (2015) Detection of a new cfr-like gene, cfr(B), in Enterococcus faecium isolates recovered from human specimens in the United States as part of the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother 59(10):6256–6261. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Diep DB, Skaugen M, Salehian Z, Holo H, Nes IF (2007) Common mechanisms of target cell recognition and immunity for class II bacteriocins. Proc Natl Acad Sci U S A 104(7):2384–2389. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Dina J, Malbruny B, Leclercq R (2003) Nonsense mutations in the lsa-like gene in Enterococcus faecalis isolates susceptible to lincosamides and Streptogramins A. Antimicrob Agents Chemother 47(7):2307–2309CrossRefGoogle Scholar
  37. 37.
    Dobbs TE, Patel M, Waites KB, Moser SA, Stamm AM, Hoesley CJ (2006) Nosocomial spread of Enterococcus faecium resistant to vancomycin and linezolid in a tertiary care medical center. J Clin Microbiol 44(9):3368–3370. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Domenech O, Francius G, Tulkens PM, Van Bambeke F, Dufrene Y, Mingeot-Leclercq MP (2009) Interactions of oritavancin, a new lipoglycopeptide derived from vancomycin, with phospholipid bilayers: effect on membrane permeability and nanoscale lipid membrane organization. Biochim Biophys Acta 1788(9):1832–1840. CrossRefPubMedGoogle Scholar
  39. 39.
    Donskey CJ (2004) The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clin Infect Dis 39(2):219–226. CrossRefPubMedGoogle Scholar
  40. 40.
    Donskey CJ, Hanrahan JA, Hutton RA, Rice LB (2000) Effect of parenteral antibiotic administration on the establishment of colonization with vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract. J Infect Dis 181(5):1830–1833. CrossRefPubMedGoogle Scholar
  41. 41.
    Dupont H, Vael C, Muller-Serieys C, Chosidow D, Mantz J, Marmuse JP, Andremont A, Goossens H, Desmonts JM (2008) Prospective evaluation of virulence factors of enterococci isolated from patients with peritonitis: impact on outcome. Diagn Microbiol Infect Dis 60(3):247–253. CrossRefPubMedGoogle Scholar
  42. 42.
    Edmond MB, Ober JF, Dawson JD, Weinbaum DL, Wenzel RP (1996) Vancomycin-resistant enterococcal bacteremia: natural history and attributable mortality. Clin Infect Dis 23(6):1234–1239CrossRefGoogle Scholar
  43. 43.
    Ekblad B, Nissen-Meyer J, Kristensen T (2017) Whole-genome sequencing of mutants with increased resistance against the two-peptide bacteriocin plantaricin JK reveals a putative receptor and potential docking site. PLoS One 12(9):e0185279. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Ellermeier CD, Losick R (2006) Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis. Genes Dev 20(14):1911–1922. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Fantin B, Leclercq R, Garry L, Carbon C (1997) Influence of inducible cross-resistance to macrolides, lincosamides, and streptogramin B-type antibiotics in Enterococcus faecium on activity of quinupristin-dalfopristin in vitro and in rabbits with experimental endocarditis. Antimicrob Agents Chemother 41(5):931–935CrossRefGoogle Scholar
  46. 46.
    Frank KL, Barnes AM, Grindle SM, Manias DA, Schlievert PM, Dunny GM (2012) Use of recombinase-based in vivo expression technology to characterize Enterococcus faecalis gene expression during infection identifies in vivo-expressed antisense RNAs and implicates the protease Eep in pathogenesis. Infect Immun 80(2):539–549. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Gabrielsen C, Brede DA, Nes IF, Diep DB (2014) Circular bacteriocins: biosynthesis and mode of action. Appl Environ Microbiol 80(22):6854–6862. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Garcia De Gonzalo CV, Denham EL, Mars RA, Stulke J, van der Donk WA, van Dijl JM (2015) The phosphoenolpyruvate:sugar phosphotransferase system is involved in sensitivity to the glucosylated bacteriocin sublancin. Antimicrob Agents Chemother 59(11):6844–6854. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Graham CE, Cruz MR, Garsin DA, Lorenz MC (2017) Enterococcus faecalis bacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence of Candida albicans. Proc Natl Acad Sci U S A 114(17):4507–4512. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Greer ND (2006) Tigecycline (Tygacil): the first in the glycylcycline class of antibiotics. Proc (Bayl Univ Med Cent) 19(2):155–161CrossRefGoogle Scholar
  51. 51.
    Hanchi H, Hammami R, Gingras H, Kourda R, Bergeron MG, Ben Hamida J, Ouellette M, Fliss I (2017) Inhibition of MRSA and of Clostridium difficile by durancin 61A: synergy with bacteriocins and antibiotics. Future Microbiol 12:205–212. CrossRefPubMedGoogle Scholar
  52. 52.
    Hayes K, Cotter L, O'Halloran F (2019) In-vitro synergistic activity of erythromycin and nisin against clinical Group B Streptococcus isolates. J Appl Microbiol. CrossRefGoogle Scholar
  53. 53.
    Hefazi M, Damlaj M, Alkhateeb HB, Partain DK, Patel R, Razonable RR, Gastineau DA, Al-Kali A, Hashmi SK, Hogan WJ, Litzow MR, Patnaik MM (2016) Vancomycin-resistant Enterococcus colonization and bloodstream infection: prevalence, risk factors, and the impact on early outcomes after allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. Transpl Infect Dis 18(6):913–920. CrossRefPubMedGoogle Scholar
  54. 54.
    Hegstad K, Mikalsen T, Coque TM, Werner G, Sundsfjord A (2010) Mobile genetic elements and their contribution to the emergence of antimicrobial resistant Enterococcus faecalis and Enterococcus faecium. Clin Microbiol Infect 16(6):541–554. CrossRefPubMedGoogle Scholar
  55. 55.
    Heikens E, Bonten MJ, Willems RJ (2007) Enterococcal surface protein Esp is important for biofilm formation of Enterococcus faecium E1162. J Bacteriol 189(22):8233–8240. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Heikens E, Leendertse M, Wijnands LM, van Luit-Asbroek M, Bonten MJ, van der Poll T, Willems RJ (2009) Enterococcal surface protein Esp is not essential for cell adhesion and intestinal colonization of Enterococcus faecium in mice. BMC Microbiol 9:19. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Hendrickx AP, van Wamel WJ, Posthuma G, Bonten MJ, Willems RJ (2007) Five genes encoding surface-exposed LPXTG proteins are enriched in hospital-adapted Enterococcus faecium clonal complex 17 isolates. J Bacteriol 189(22):8321–8332. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Higgins DL, Chang R, Debabov DV, Leung J, Wu T, Krause KM, Sandvik E, Hubbard JM, Kaniga K, Schmidt DE Jr, Gao Q, Cass RT, Karr DE, Benton BM, Humphrey PP (2005) Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 49(3):1127–1134. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Ho TD, Ellermeier CD (2012) Extra cytoplasmic function sigma factor activation. Curr Opin Microbiol 15(2):182–188. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Ispirli H, Demirbas F, Dertli E (2015) Characterization of functional properties of Enterococcus faecium strains isolated from human gut. Can J Microbiol 61(11):861–870. CrossRefPubMedGoogle Scholar
  61. 61.
    Johnsen L, Fimland G, Eijsink V, Nissen-Meyer J (2000) Engineering increased stability in the antimicrobial peptide pediocin PA-1. Appl Environ Microbiol 66(11):4798–4802. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Johnson JA, Feeney ER, Kubiak DW, Corey GR (2015) Prolonged use of oritavancin for vancomycin-resistant Enterococcus faecium prosthetic valve endocarditis. Open Forum Infect Dis 2(4):ofv156. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Jordan S, Hutchings MI, Mascher T (2008) Cell envelope stress response in Gram-positive bacteria. FEMS Microbiol Rev 32(1):107–146. CrossRefPubMedGoogle Scholar
  64. 64.
    Kamboj M, Cohen N, Gilhuley K, Babady NE, Seo SK, Sepkowitz KA (2011) Emergence of daptomycin-resistant VRE: experience of a single institution. Infect Control Hosp Epidemiol 32(4):391–394. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Kanehara K, Akiyama Y, Ito K (2001) Characterization of the yaeL gene product and its S2P-protease motifs in Escherichia coli. Gene 281(1–2):71–79CrossRefGoogle Scholar
  66. 66.
    Kara A, Devrim I, Bayram N, Katipoglu N, Kiran E, Oruc Y, Demiray N, Apa H, Gulfidan G (2015) Risk of vancomycin-resistant enterococci bloodstream infection among patients colonized with vancomycin-resistant enterococci. Braz J Infect Dis 19(1):58–61. CrossRefPubMedGoogle Scholar
  67. 67.
    Kristich CJ, Rice LB, Arias CA (2014) Enterococcal infection—treatment and antibiotic resistance. In: Gilmore MS, Clewell DB, Ike Y, Shankar N (eds) Enterococci: from commensals to leading causes of drug resistant infection, Boston.
  68. 68.
    Lam MM, Seemann T, Bulach DM, Gladman SL, Chen H, Haring V, Moore RJ, Ballard S, Grayson ML, Johnson PD, Howden BP, Stinear TP (2012) Comparative analysis of the first complete Enterococcus faecium genome. J Bacteriol 194(9):2334–2341. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Leavis HL, Willems RJ, van Wamel WJ, Schuren FH, Caspers MP, Bonten MJ (2007) Insertion sequence-driven diversification creates a globally dispersed emerging multiresistant subspecies of E. faecium. PLoS Pathog 3(1):e7. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Leendertse M, Heikens E, Wijnands LM, van Luit-Asbroek M, Teske GJ, Roelofs JJ, Bonten MJ, van der Poll T, Willems RJ (2009) Enterococcal surface protein transiently aggravates Enterococcus faecium-induced urinary tract infection in mice. J Infect Dis 200(7):1162–1165. CrossRefPubMedGoogle Scholar
  71. 71.
    Lindenstrauss AG, Pavlovic M, Bringmann A, Behr J, Ehrmann MA, Vogel RF (2011) Comparison of genotypic and phenotypic cluster analyses of virulence determinants and possible role of CRISPR elements towards their incidence in Enterococcus faecalis and Enterococcus faecium. Syst Appl Microbiol 34(8):553–560. CrossRefPubMedGoogle Scholar
  72. 72.
    Lopez F, Culebras E, Betriu C, Rodriguez-Avial I, Gomez M, Picazo JJ (2010) Antimicrobial susceptibility and macrolide resistance genes in Enterococcus faecium with reduced susceptibility to quinupristin-dalfopristin: level of quinupristin-dalfopristin resistance is not dependent on erm(B) attenuator region sequence. Diagn Microbiol Infect Dis 66(1):73–77. CrossRefPubMedGoogle Scholar
  73. 73.
    Maraki S, Samonis G, Dimopoulou D, Mantadakis E (2014) Susceptibility of glycopeptide-resistant enterococci to linezolid, quinupristin/dalfopristin, tigecycline and daptomycin in a tertiary Greek hospital. Infect Chemother 46(4):253–256. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Mave V, Garcia-Diaz J, Islam T, Hasbun R (2009) Vancomycin-resistant enterococcal bacteraemia: is daptomycin as effective as linezolid? J Antimicrob Chemother 64(1):175–180. CrossRefPubMedGoogle Scholar
  75. 75.
    McLaughlin M, Malczynski M, Qi C, Barajas G, Radetski J, Zembower T, Scheetz MH (2013) Virulence of vancomycin-resistant Enterococcus faecium according to linezolid resistance and clinical outbreak status. Antimicrob Agents Chemother 57(8):3923–3927. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Mendes RE, Deshpande LM, Jones RN (2014) Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms. Drug Resist Updat 17(1–2):1–12. CrossRefPubMedGoogle Scholar
  77. 77.
    Mendes RE, Flamm RK, Hogan PA, Ross JE, Jones RN (2014) Summary of linezolid activity and resistance mechanisms detected during the 2012 LEADER surveillance program for the United States. Antimicrob Agents Chemother 58(2):1243–1247. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Millette M, Cornut G, Dupont C, Shareck F, Archambault D, Lacroix M (2008) Capacity of human nisin- and pediocin-producing lactic acid bacteria to reduce intestinal colonization by vancomycin-resistant enterococci. Appl Environ Microbiol 74(7):1997–2003. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Miyazaki S, Fujikawa T, Kobayashi I, Matsumoto T, Tateda K, Yamaguchi K (2001) Development of systemic bacteraemia after oral inoculation of vancomycin-resistant enterococci in mice. J Med Microbiol 50(8):695–701. CrossRefPubMedGoogle Scholar
  80. 80.
    Moise PA, Hershberger E, Amodio-Groton MI, Lamp KC (2009) Safety and clinical outcomes when utilizing high-dose (> or = 8 mg/kg) daptomycin therapy. Ann Pharmacother 43(7):1211–1219. CrossRefPubMedGoogle Scholar
  81. 81.
    Munch D, Engels I, Muller A, Reder-Christ K, Falkenstein-Paul H, Bierbaum G, Grein F, Bendas G, Sahl HG, Schneider T (2015) Structural variations of the cell wall precursor lipid II and their influence on binding and activity of the lipoglycopeptide antibiotic oritavancin. Antimicrob Agents Chemother 59(2):772–781. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Murray BE (2000) Vancomycin-resistant enterococcal infections. N Engl J Med 342(10):710–721. CrossRefPubMedGoogle Scholar
  83. 83.
    Nallapareddy SR, Weinstock GM, Murray BE (2003) Clinical isolates of Enterococcus faecium exhibit strain-specific collagen binding mediated by Acm, a new member of the MSCRAMM family. Mol Microbiol 47(6):1733–1747CrossRefGoogle Scholar
  84. 84.
    O'Driscoll T, Crank CW (2015) Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management. Infect Drug Resist 8:217–230. CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Oppegard C, Kjos M, Veening JW, Nissen-Meyer J, Kristensen T (2016) A putative amino acid transporter determines sensitivity to the two-peptide bacteriocin plantaricin JK. Microbiologyopen 5(4):700–708. CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Ovchinnikov KV, Chi H, Mehmeti I, Holo H, Nes IF, Diep DB (2016) Novel group of leaderless multipeptide bacteriocins from Gram-positive bacteria. Appl Environ Microbiol 82(17):5216–5224. CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Ovchinnikov KV, Kristiansen PE, Straume D, Jensen MS, Aleksandrzak-Piekarczyk T, Nes IF, Diep DB (2017) The leaderless bacteriocin enterocin K1 is highly potent against Enterococcus faecium: a study on structure, target spectrum and receptor. Front Microbiol 8:774. CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Ovchinnikov KV, Kristiansen PE, Uzelac G, Topisirovic L, Kojic M, Nissen-Meyer J, Nes IF, Diep DB (2014) Defining the structure and receptor binding domain of the leaderless bacteriocin LsbB. J Biol Chem 289(34):23838–23845. CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Palmer KL, Kos VN, Gilmore MS (2010) Horizontal gene transfer and the genomics of enterococcal antibiotic resistance. Curr Opin Microbiol 13(5):632–639. CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Patel R, Gallagher JC (2015) Vancomycin-resistant enterococcal bacteremia pharmacotherapy. Ann Pharmacother 49(1):69–85. CrossRefPubMedGoogle Scholar
  91. 91.
    Patti GJ, Kim SJ, Yu TY, Dietrich E, Tanaka KS, Parr TR Jr, Far AR, Schaefer J (2009) Vancomycin and oritavancin have different modes of action in Enterococcus faecium. J Mol Biol 392(5):1178–1191. CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Perez RH, Zendo T, Sonomoto K (2014) Novel bacteriocins from lactic acid bacteria (LAB): various structures and applications. Microb Cell Fact 13(Suppl 1):S3. CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Phumisantiphong U, Siripanichgon K, Reamtong O, Diraphat P (2017) A novel bacteriocin from Enterococcus faecalis 478 exhibits a potent activity against vancomycin-resistant enterococci. PLoS One 12(10):e0186415. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Prematunge C, MacDougall C, Johnstone J, Adomako K, Lam F, Robertson J, Garber G (2016) VRE and VSE bacteremia outcomes in the era of effective VRE therapy: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 37(1):26–35. CrossRefPubMedGoogle Scholar
  95. 95.
    Pultz NJ, Shankar N, Baghdayan AS, Donskey CJ (2005) Enterococcal surface protein Esp does not facilitate intestinal colonization or translocation of Enterococcus faecalis in clindamycin-treated mice. FEMS Microbiol Lett 242(2):217–219. CrossRefPubMedGoogle Scholar
  96. 96.
    Pultz NJ, Vesterlund S, Ouwehand AC, Donskey CJ (2006) Adhesion of vancomycin-resistant enterococcus to human intestinal mucus. Curr Microbiol 52(3):221–224. CrossRefPubMedGoogle Scholar
  97. 97.
    Purohit G, Gaind R, Dawar R, Verma PK, Aggarwal KC, Sardana R, Deb M (2017) Characterization of vancomycin resistant enterococci in hospitalized patients and role of gut colonization. J Clin Diagn Res 11(9):DC01–DC05. CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Raad II, Hanna HA, Hachem RY, Dvorak T, Arbuckle RB, Chaiban G, Rice LB (2004) Clinical-use-associated decrease in susceptibility of vancomycin-resistant Enterococcus faecium to linezolid: a comparison with quinupristin-dalfopristin. Antimicrob Agents Chemother 48(9):3583–3585. CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Raivio TL, Silhavy TJ (2001) Periplasmic stress and ECF sigma factors. Annu Rev Microbiol 55:591–624. CrossRefPubMedGoogle Scholar
  100. 100.
    Ramu R, Shirahatti PS, Devi AT, Prasad A, J K, M S L, F Z, B LD, M N N (2015) Bacteriocins and their applications in food preservation. Crit Rev Food Sci Nutr 0.
  101. 101.
    Rathnayake IU, Hargreaves M, Huygens F (2012) Antibiotic resistance and virulence traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates. Syst Appl Microbiol 35(5):326–333. CrossRefPubMedGoogle Scholar
  102. 102.
    Riley MA, Wertz JE (2002) Bacteriocins: evolution, ecology, and application. Annu Rev Microbiol 56:117–137. CrossRefPubMedGoogle Scholar
  103. 103.
    Roger C, Roberts JA, Muller L (2018) Clinical pharmacokinetics and pharmacodynamics of oxazolidinones. Clin Pharmacokinet 57(5):559–575. CrossRefPubMedGoogle Scholar
  104. 104.
    Rosa RG, Schwarzbold AV, Dos Santos RP, Turra EE, Machado DP, Goldani LZ (2014) Vancomycin-resistant Enterococcus faecium bacteremia in a tertiary care hospital: epidemiology, antimicrobial susceptibility, and outcome. Biomed Res Int 2014:958469. CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Rosko AE, Corriveau M, Suwantarat N, Arfons L, Treasure M, Parker P, Jacobs M, Fu P, Salata R, Lazarus HM (2014) Vancomycin-resistant enterococci infection: not just for the transplanted. Leuk Lymphoma 55(6):1320–1325. CrossRefPubMedGoogle Scholar
  106. 106.
    Sader HS, Farrell DJ, Flamm RK, Jones RN (2014) Daptomycin activity tested against 164457 bacterial isolates from hospitalised patients: summary of 8 years of a worldwide surveillance programme (2005–2012). Int J Antimicrob Agents 43(5):465–469. CrossRefPubMedGoogle Scholar
  107. 107.
    Sader HS, Jones RN (2009) Antimicrobial susceptibility of Gram-positive bacteria isolated from US medical centers: results of the Daptomycin surveillance program (2007–2008). Diagn Microbiol Infect Dis 65(2):158–162. CrossRefPubMedGoogle Scholar
  108. 108.
    Sahm DF, Deane J, Bien PA, Locke JB, Zuill DE, Shaw KJ, Bartizal KF (2015) Results of the surveillance of Tedizolid activity and resistance program: in vitro susceptibility of Gram-positive pathogens collected in 2011 and 2012 from the United States and Europe. Diagn Microbiol Infect Dis 81(2):112–118. CrossRefPubMedGoogle Scholar
  109. 109.
    Saleh-Mghir A, Lefort A, Petegnief Y, Dautrey S, Vallois JM, Le Guludec D, Carbon C, Fantin B (1999) Activity and diffusion of LY333328 in experimental endocarditis due to vancomycin-resistant Enterococcus faecalis. Antimicrob Agents Chemother 43(1):115–120CrossRefGoogle Scholar
  110. 110.
    Salgado CD, Farr BM (2003) Outcomes associated with vancomycin-resistant enterococci: a meta-analysis. Infect Control Hosp Epidemiol 24(9):690–698. CrossRefPubMedGoogle Scholar
  111. 111.
    Sillanpaa J, Nallapareddy SR, Singh KV, Prakash VP, Fothergill T, Ton-That H, Murray BE (2010) Characterization of the ebp(fm) pilus-encoding operon of Enterococcus faecium and its role in biofilm formation and virulence in a murine model of urinary tract infection. Virulence 1(4):236–246CrossRefGoogle Scholar
  112. 112.
    Silva CCG, Silva SPM, Ribeiro SC (2018) Application of bacteriocins and protective cultures in dairy food preservation. Front Microbiol 9:594. CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Singh AP, Prabha V, Rishi P (2013) Value addition in the efficacy of conventional antibiotics by nisin against Salmonella. PLoS One 8(10):e76844. CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Steckbeck JD, Deslouches B, Montelaro RC (2014) Antimicrobial peptides: new drugs for bad bugs? Expert Opin Biol Ther 14(1):11–14. CrossRefPubMedGoogle Scholar
  115. 115.
    Stiefel U, Pultz NJ, Helfand MS, Donskey CJ (2004) Increased susceptibility to vancomycin-resistant Enterococcus intestinal colonization persists after completion of anti-anaerobic antibiotic treatment in mice. Infect Control Hosp Epidemiol 25(5):373–379. CrossRefPubMedGoogle Scholar
  116. 116.
    Surveillance of antimicrobial resistance in Europe 2016. (2017). Surveillance of antimicrobial resistance in Europe 2016Google Scholar
  117. 117.
    Thomas VM, Brown RM, Ashcraft DS, Pankey GA (2019) Synergistic effect between nisin and polymyxin B against pandrug-resistant and extensively drug-resistant Acinetobacter baumannii. Int J Antimicrob Agents 53(5):663–668. CrossRefPubMedGoogle Scholar
  118. 118.
    Tran TT, Panesso D, Mishra NN, Mileykovskaya E, Guan Z, Munita JM, Reyes J, Diaz L, Weinstock GM, Murray BE, Shamoo Y, Dowhan W, Bayer AS, Arias CA (2013) Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids. MBio 4(4).
  119. 119.
    Twilla JD, Finch CK, Usery JB, Gelfand MS, Hudson JQ, Broyles JE (2012) Vancomycin-resistant Enterococcus bacteremia: an evaluation of treatment with linezolid or daptomycin. J Hosp Med 7(3):243–248. CrossRefPubMedGoogle Scholar
  120. 120.
    Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M, Viale A, Socci ND, van den Brink MRM, Kamboj M, Pamer EG (2010) Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest 120(12):4332–4341. CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    van Staden AD, Brand AM, Dicks LM (2012) Nisin F-loaded brushite bone cement prevented the growth of Staphylococcus aureus in vivo. J Appl Microbiol 112(4):831–840. CrossRefPubMedGoogle Scholar
  122. 122.
    van Staden AP, Heunis T, Smith C, Deane S, Dicks LM (2016) Efficacy of lantibiotic treatment of Staphylococcus aureus-induced skin infections, monitored by in vivo bioluminescent imaging. Antimicrob Agents Chemother 60(7):3948–3955. CrossRefPubMedCentralGoogle Scholar
  123. 123.
    Vergis EN, Hayden MK, Chow JW, Snydman DR, Zervos MJ, Linden PK, Wagener MM, Schmitt B, Muder RR (2001) Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia: a prospective multicenter study. Ann Intern Med 135(7):484–492CrossRefGoogle Scholar
  124. 124.
    Willems RJ, Top J, van Santen M, Robinson DA, Coque TM, Baquero F, Grundmann H, Bonten MJ (2005) Global spread of vancomycin-resistant Enterococcus faecium from distinct nosocomial genetic complex. Emerg Infect Dis 11(6):821–828. CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Wolska KI, Grzes K, Kurek A (2012) Synergy between novel antimicrobials and conventional antibiotics or bacteriocins. Pol J Microbiol 61(2):95–104PubMedGoogle Scholar
  126. 126.
    Yang SC, Lin CH, Sung CT, Fang JY (2014) Antibacterial activities of bacteriocins: application in foods and pharmaceuticals. Front Microbiol 5:241. CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Yim J, Smith JR, Rybak MJ (2017) Role of combination antimicrobial therapy for vancomycin-resistant Enterococcus faecium infections: review of the current evidence. Pharmacotherapy 37(5):579–592. CrossRefPubMedGoogle Scholar
  128. 128.
    Zasowski EJ, Claeys KC, Lagnf AM, Davis SL, Rybak MJ (2016) Time is of the essence: the impact of delayed antibiotic therapy on patient outcomes in hospital-onset enterococcal bloodstream infections. Clin Infect Dis 62(10):1242–1250. CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Zhou L, van Heel AJ, Montalban-Lopez M, Kuipers OP (2016) Potentiating the activity of nisin against Escherichia coli. Front Cell Dev Biol 4:7. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry, Biotechnology and Food ScienceNorwegian University of Life SciencesÅsNorway
  2. 2.Section of Pharmaceutics and Social Pharmacy, Department of PharmacyUniversity of OsloOsloNorway

Personalised recommendations