Enterococcus faecalis explained

Enterococcus faecalis – formerly classified as part of the group D Streptococcus system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans.[1] [2] Like other species in the genus Enterococcus, E. faecalis is found in healthy humans and can be used as a probiotic. The probiotic strains such as Symbioflor1 and EF-2001 are characterized by the lack of specific genes related to drug resistance and pathogenesis.[3] As an opportunistic pathogen, E. faecalis can cause life-threatening infections, especially in the nosocomial (hospital) environment, where the naturally high levels of antibiotic resistance found in E. faecalis contribute to its pathogenicity.E. faecalis has been frequently found in reinfected, root canal-treated teeth in prevalence values ranging from 30% to 90% of the cases.[4] Re-infected root canal-treated teeth are about nine times more likely to harbor E. faecalis than cases of primary infections.[5]

Physiology

E. faecalis is a nonmotile microbe; it ferments glucose without gas production, and does not produce a catalase reaction with hydrogen peroxide. It produces a reduction of litmus milk, but does not liquefy gelatin. It shows consistent growth throughout nutrient broth which is consistent with being a facultative anaerobe. It catabolizes a variety of energy sources, including glycerol, lactate, malate, citrate, arginine, agmatine, and many keto acids. Enterococci survive very harsh environments, including extremely alkaline pH (9.6) and salt concentrations. They resist bile salts, detergents, heavy metals, ethanol, azide, and desiccation. They can grow in the range of 10 to 45 °C and survive at temperatures of 60 °C for 30 min.

Pathogenesis

E. faecalis is found in most healthy individuals, but can cause endocarditis and sepsis, urinary tract infections (UTIs), meningitis, and other infections in humans.[6] [7] Several virulence factors are thought to contribute to E. faecalis infections. A plasmid-encoded hemolysin, called the cytolysin, is important for pathogenesis in animal models of infection, and the cytolysin in combination with high-level gentamicin resistance is associated with a five-fold increase in risk of death in human bacteremia patients.[8] [9] [10] A plasmid-encoded adhesin[11] called "aggregation substance" is also important for virulence in animal models of infection.[9] [12]

E. faecalis contains a tyrosine decarboxylase enzyme capable of decarboxylating L-DOPA, a crucial drug in the treatment of Parkinson's disease. If L-DOPA is decarboxylated in the gut microbiome, it cannot pass through the blood-brain barrier and be decarboxylated in the brain to become dopamine.[13]

Antibacterial resistance

Multi drug resistance

See main article: Vancomycin-resistant Enterococcus.

E. faecalis is usually resistant to many commonly used antimicrobial agents (aminoglycosides, aztreonam and quinolones. The resistance is mediated by the presence of multiple genes related to drug resistance in the chromosome or plasmid.

Resistance to vancomycin in E. faecalis is becoming more common.[14] [15] Treatment options for vancomycin-resistant E. faecalis include nitrofurantoin (in the case of uncomplicated UTIs),[16] linezolid, quinupristin, tigecycline and daptomycin, although ampicillin is preferred if the bacteria are susceptible.[17] Quinupristin/dalfopristin can be used to treat Enterococcus faecium but not E. faecalis.

In root-canal treatments, NaOCl and chlorhexidine (CHX) are used to fight E. faecalis before isolating the canal. However, recent studies determined that NaOCl or CHX showed low ability to eliminate E. faecalis.[18]

Combined drug therapies

According to one study combined drug therapy has shown some efficacy in cases of severe infections (e.g. heart valves infections) against susceptible strains of E. faecalis. Ampicillin- and vancomycin-sensitive E. faecalis (lacking high-level resistance to aminoglycosides) strains can be treated by gentamicin and ampicillin antibiotics. A less nephrotoxic combination of ampicillin and ceftriaxone (even though E. faecalis is resistant to cephalosporins, ceftriaxone is working synergistically with ampicillin) may be used alternatively for ampicillin-susceptible E. faecalis.[19]

Daptomycin or linezolid may also show efficacy in case ampicillin and vancomycin resistance.[19]

A combination of penicillin and streptomycin therapy was used in the past.[19]

Tedizolid, telavancin, dalbavancin, and oritavancin antibiotics are FDA approved as treatments against EF.[20]

Survival and virulence factors

DNA repair

In human blood, E. faecalis is subjected to conditions that damage its DNA, but this damage can be tolerated by the use of DNA repair processes.[26] This damage tolerance depends, in part, on the two protein complex RexAB, encoded by the E. faecalis genome, that is employed in the recombinational repair of DNA double-strand breaks.[26]

Biofilm formation

The ability of E. faecalis to form biofilms contributes to its capacity to survive in extreme environments, and facilitates its involvement in persistent bacterial infection, particularly in the case of multi-drug resistant strains.[27] Biofilm formation in E. faecalis is associated with DNA release, and such release has emerged as a fundamental aspect of biofilm formation.[27] Conjugative plasmid DNA transfer in E. faecalis is enhanced by the release of peptide sex pheromones.[28]

Historical

Prior to 1984, enterococci were members of the genus Streptococcus; thus, E. faecalis was known as Streptococcus faecalis.[29]

In 2013, a combination of cold denaturation and NMR spectroscopy was used to show detailed insights into the unfolding of the E. faecalis homodimeric repressor protein CylR2.[30]

Genome structure

The E. faecalis genome consists of 3.22 million base pairs with 3,113 protein-coding genes.[31]

Treatment research

Glutamate racemase, hydroxymethylglutaryl-CoA synthase, diphosphomevalonate decarboxylase, topoisomerase DNA gyrase B, D-alanine—D-serine ligase, alanine racemase, phosphate acetyltransferase, NADH peroxidase,Phosphopantetheine adenylyltransferase (PPAT), acyl carrier protein, 3‐Dehydroquinate dehydratase and Deoxynucleotide triphosphate triphosphohydrolase are all potential molecules that may be used for treating EF infections.[20]

Bacillus haynesii CD223 and Advenella mimigardefordensis SM421 can inhibit the growth of Enterococcus faecalis.[32]

Small RNA

Bacterial small RNAs play important roles in many cellular processes; 11 small RNAs have been experimentally characterised in E. faecalis V583 and detected in various growth phases.[33] Five of them have been shown to be involved in stress response and virulence.[34]

A genome-wide sRNA study suggested that some sRNAs are linked to the antibiotic resistance and stress response in another Enteroccocus: E. faecium.[35]

Swimming pool contamination

Indicators of recreational water quality

Because E. faecalis is a common fecal bacterium in humans, recreational water facilities (such as swimming pools and beaches that allow visitors to swim in the ocean) often measure the concentrations of E. faecalis to assess the quality of their water. The higher the concentration, the worse the quality of the water. The practice of using E. faecalis as a quality indicator is recommended by the World Health Organization (WHO) as well as many developed countries after multiple studies have reported that higher concentrations of E. faecalis correlate to greater percentages of swimmer illness. This correlation exists in both freshwater and marine environments, so measuring E. faecalis concentrations to determine water quality applies to all recreational waters. However, the correlation does not imply that E. faecalis is the ultimate cause of swimmer illnesses. One alternative explanation is that higher levels of E. faecalis correspond to higher levels of human viruses, which cause sickness in swimmers. Although this claim may sound plausible, there is currently little evidence that establishes the link between E. faecalis and human virus (or other pathogens) levels. Thus, despite the strong correlation between E. faecalis and water quality, more research is needed to determine the causal relationship of this correlation.

Human shedding

For recreational waters near or at beaches, E. faecalis can come from multiple sources, such as the sand and human bodies. Determining the sources of E. faecalis is crucial for controlling water contamination, though often the sources are non-point (for example, human bathers). As such, one study looked at how much E. faecalis is shed from bathers at the beach. The first group of participants immersed themselves in a large pool with marine water for 4 cycles of 15 minutes, both with and without contacting sand beforehand. The result shows a decrease in E. faecalis levels for each cycle, suggesting that people shed the most bacteria when they first get into a pool. The second group of participants entered small, individual pools after contact with beach sand, and researchers collected data on how much E. faecalis in the pool came from the sand brought by the participants and how much came from the participants’ shedding. The result shows that E. faecalis from the sand is very small compared to that from human shedding. Although this result may not apply to all sand types, a tentative conclusion is that human shedding is a major non-point source of E. faecalis in recreational waters.[36]

See also

External links

Notes and References

  1. de Almeida CV, Taddei A, Amedei A . The controversial role of Enterococcus faecalis in colorectal cancer . Therapeutic Advances in Gastroenterology . 11 . 1756284818783606 . 2018-01-01 . 30013618 . 6044108 . 10.1177/1756284818783606 . SAGE Publications .
  2. Book: Ryan KJ, Ray CG . Sherris Medical Microbiology . 4th . 294–295 . McGraw Hill . 2004 . 0-8385-8529-9 .
  3. Panthee S, Paudel A, Hamamoto H, Ogasawara AA, Iwasa T, Blom J, Sekimizu K . Complete genome sequence and comparative genomic analysis of Enterococcus faecalis EF-2001, a probiotic bacterium . Genomics . 113 . 3 . 1534–1542 . May 2021 . 33771633 . 10.1016/j.ygeno.2021.03.021 . free .
  4. Molander A, Reit C, Dahlén G, Kvist T . Microbiological status of root-filled teeth with apical periodontitis . International Endodontic Journal . 31 . 1 . 1–7 . January 1998 . 9823122 . 10.1046/j.1365-2591.1998.t01-1-00111.x .
  5. Rôças IN, Siqueira JF, Santos KR . Association of Enterococcus faecalis with different forms of periradicular diseases . Journal of Endodontics . 30 . 5 . 315–320 . May 2004 . 15107642 . 10.1097/00004770-200405000-00004 .
  6. Murray BE . The life and times of the Enterococcus . Clinical Microbiology Reviews . 3 . 1 . 46–65 . January 1990 . 2404568 . 358140 . 10.1128/cmr.3.1.46 .
  7. Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK . NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007 . Infection Control and Hospital Epidemiology . 29 . 11 . 996–1011 . November 2008 . 18947320 . 10.1086/591861 . 205988392 . National Healthcare Safety Network Team . Participating National Healthcare Safety Network Facilities .
  8. Huycke MM, Spiegel CA, Gilmore MS . Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis . Antimicrobial Agents and Chemotherapy . 35 . 8 . 1626–1634 . August 1991 . 1929336 . 245231 . 10.1128/aac.35.8.1626 .
  9. Chow JW, Thal LA, Perri MB, Vazquez JA, Donabedian SM, Clewell DB, Zervos MJ . Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis . Antimicrobial Agents and Chemotherapy . 37 . 11 . 2474–2477 . November 1993 . 8285637 . 192412 . 10.1128/aac.37.11.2474 .
  10. Ike Y, Hashimoto H, Clewell DB . Hemolysin of Streptococcus faecalis subspecies zymogenes contributes to virulence in mice . Infection and Immunity . 45 . 2 . 528–530 . August 1984 . 6086531 . 263283 . 10.1128/IAI.45.2.528-530.1984 .
  11. Kreft B, Marre R, Schramm U, Wirth R . Aggregation substance of Enterococcus faecalis mediates adhesion to cultured renal tubular cells . Infection and Immunity . 60 . 1 . 25–30 . January 1992 . 1729187 . 257498 . 10.1128/IAI.60.1.25-30.1992 .
  12. Hirt H, Schlievert PM, Dunny GM . In vivo induction of virulence and antibiotic resistance transfer in Enterococcus faecalis mediated by the sex pheromone-sensing system of pCF10 . Infection and Immunity . 70 . 2 . 716–723 . February 2002 . 11796604 . 127697 . 10.1128/iai.70.2.716-723.2002 .
  13. Maini Rekdal V, Bess EN, Bisanz JE, Turnbaugh PJ, Balskus EP . Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism . Science . 364 . 6445 . eaau6323 . June 2019 . 31196984 . 7745125 . 10.1126/science.aau6323 .
  14. Amyes SG . Enterococci and streptococci . International Journal of Antimicrobial Agents . 29 . Suppl 3 . S43–S52 . May 2007 . 17659211 . 10.1016/S0924-8579(07)72177-5 .
  15. Courvalin P . Vancomycin resistance in gram-positive cocci . Clinical Infectious Diseases . 42 . Suppl 1 . S25–S34 . January 2006 . 16323116 . 10.1086/491711 . free .
  16. Zhanel GG, Hoban DJ, Karlowsky JA . Nitrofurantoin is active against vancomycin-resistant enterococci . Antimicrobial Agents and Chemotherapy . 45 . 1 . 324–326 . January 2001 . 11120989 . 90284 . 10.1128/AAC.45.1.324-326.2001 .
  17. Arias CA, Contreras GA, Murray BE . Management of multidrug-resistant enterococcal infections . Clinical Microbiology and Infection . 16 . 6 . 555–562 . June 2010 . 20569266 . 3686902 . 10.1111/j.1469-0691.2010.03214.x .
  18. Estrela C, Silva JA, de Alencar AH, Leles CR, Decurcio DA . Efficacy of sodium hypochlorite and chlorhexidine against Enterococcus faecalis--a systematic review . Journal of Applied Oral Science . 16 . 6 . 364–368 . December 2008 . 19082392 . 4327704 . 10.1590/s1678-77572008000600002 .
  19. Dubin K, Pamer EG . Enterococci and Their Interactions with the Intestinal Microbiome . Microbiology Spectrum . 5 . 6 . 309–330 . November 2014 . 29125098 . 5691600 . 10.1128/microbiolspec.BAD-0014-2016 . 978-1-55581-969-9 . Britton RA, Cani PD .
  20. Singh H, Das S, Yadav J, Srivastava VK, Jyoti A, Kaushik S . In search of novel protein drug targets for treatment of Enterococcus faecalis infections . Chemical Biology & Drug Design . 94 . 4 . 1721–1739 . October 2019 . 31260188 . 10.1111/cbdd.13582 . Wiley . 195756723 .
  21. Huycke MM, Moore D, Joyce W, Wise P, Shepard L, Kotake Y, Gilmore MS . Extracellular superoxide production by Enterococcus faecalis requires demethylmenaquinone and is attenuated by functional terminal quinol oxidases . Molecular Microbiology . 42 . 3 . 729–740 . November 2001 . 11722738 . 10.1046/j.1365-2958.2001.02638.x . 25075356 .
  22. Wang X, Huycke MM . Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells . Gastroenterology . 132 . 2 . 551–561 . February 2007 . 17258726 . 10.1053/j.gastro.2006.11.040 . free .
  23. Shabahang S, Pouresmail M, Torabinejad M . In vitro antimicrobial efficacy of MTAD and sodium hypochlorite . Journal of Endodontics . 29 . 7 . 450–452 . July 2003 . 12877261 . 10.1097/00004770-200307000-00006 .
  24. Stuart CH, Schwartz SA, Beeson TJ, Owatz CB . Enterococcus faecalis: its role in root canal treatment failure and current concepts in retreatment . Journal of Endodontics . 32 . 2 . 93–98 . February 2006 . 16427453 . 10.1016/j.joen.2005.10.049 .
  25. Jacobson RA, Wienholts K, Williamson AJ, Gaines S, Hyoju S, van Goor H, Zaborin A, Shogan BD, Zaborina O, Alverdy JC . Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets . American Journal of Physiology. Gastrointestinal and Liver Physiology . 318 . 1 . G1–G9 . January 2020 . 31604031 . 6985841 . 10.1152/ajpgi.00236.2019 .
  26. Ha KP, Clarke RS, Kim GL, Brittan JL, Rowley JE, Mavridou DA, Parker D, Clarke TB, Nobbs AH, Edwards AM . Staphylococcal DNA Repair Is Required for Infection . mBio . 11 . 6 . November 2020 . 33203752 . 7683395 . 10.1128/mBio.02288-20 .
  27. Șchiopu P, Toc DA, Colosi IA, Costache C, Ruospo G, Berar G, Gălbău ȘG, Ghilea AC, Botan A, Pană AG, Neculicioiu VS, Todea DA . An Overview of the Factors Involved in Biofilm Production by the Enterococcus Genus . Int J Mol Sci . 24 . 14 . July 2023 . 11577 . 37511337 . 10380289 . 10.3390/ijms241411577 . free .
  28. Hirt H, Greenwood-Quaintance KE, Karau MJ, Till LM, Kashyap PC, Patel R, Dunny GM . Enterococcus faecalis Sex Pheromone cCF10 Enhances Conjugative Plasmid Transfer In Vivo . mBio . 9 . 1 . February 2018 . 29440568 . 5821081 . 10.1128/mBio.00037-18 .
  29. Schleifer KH, Kilpper-Balz R . Transfer of Streptococcus faecalis and Streptococcus faecium to the Genus Enterococcus nom. rev. as Enterococcus faecalis comb. nov. and Enterococcus faecium comb. nov. . International Journal of Systematic Bacteriology . 1 January 1984 . 34 . 1 . 31–34 . 10.1099/00207713-34-1-31 . free .
  30. Jaremko M, Jaremko Ł, Kim HY, Cho MK, Schwieters CD, Giller K, Becker S, Zweckstetter M . Cold denaturation of a protein dimer monitored at atomic resolution . Nature Chemical Biology . 9 . 4 . 264–270 . April 2013 . 23396077 . 5521822 . 10.1038/nchembio.1181 .
  31. Paulsen IT, Banerjei L, Myers GS, Nelson KE, Seshadri R, Read TD, Fouts DE, Eisen JA, Gill SR, Heidelberg JF, Tettelin H, Dodson RJ, Umayam L, Brinkac L, Beanan M, Daugherty S, DeBoy RT, Durkin S, Kolonay J, Madupu R, Nelson W, Vamathevan J, Tran B, Upton J, Hansen T, Shetty J, Khouri H, Utterback T, Radune D, Ketchum KA, Dougherty BA, Fraser CM . Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis . Science . 299 . 5615 . 2071–2074 . March 2003 . 12663927 . 10.1126/science.1080613 . 45480495 . 2003Sci...299.2071P .
  32. Rahman MM, Paul SI, Rahman A, Haque MS, Ador MA, Foysal MJ, Islam MT, Rahman MM . Suppression of Streptococcosis and Modulation of the Gut Bacteriome in Nile Tilapia (Oreochromis niloticus) by the Marine Sediment Bacteria Bacillus haynesii and Advenella mimigardefordensis . Microbiology Spectrum . 10 . 6 . e0254222 . December 2022 . 36453920 . 9769507 . 10.1128/spectrum.02542-22 . Rogovskyy AS, Weththasinghe P, Rodriguez-Estrada U .
  33. Shioya K, Michaux C, Kuenne C, Hain T, Verneuil N, Budin-Verneuil A, Hartsch T, Hartke A, Giard JC . Genome-wide identification of small RNAs in the opportunistic pathogen Enterococcus faecalis V583 . PLOS ONE . 6 . 9 . e23948 . 2 September 2011 . 21912655 . 3166299 . 10.1371/journal.pone.0023948 . free . 2011PLoSO...623948S .
  34. Michaux C, Hartke A, Martini C, Reiss S, Albrecht D, Budin-Verneuil A, Sanguinetti M, Engelmann S, Hain T, Verneuil N, Giard JC . Involvement of Enterococcus faecalis small RNAs in stress response and virulence . Infection and Immunity . 82 . 9 . 3599–3611 . September 2014 . 24914223 . 4187846 . 10.1128/IAI.01900-14 .
  35. Sinel C, Augagneur Y, Sassi M, Bronsard J, Cacaci M, Guérin F, Sanguinetti M, Meignen P, Cattoir V, Felden B . Small RNAs in vancomycin-resistant Enterococcus faecium involved in daptomycin response and resistance . Scientific Reports . 7 . 1 . 11067 . September 2017 . 28894187 . 5593968 . 10.1038/s41598-017-11265-2 . 2017NatSR...711067S .
  36. Elmir SM, Wright ME, Abdelzaher A, Solo-Gabriele HM, Fleming LE, Miller G, Rybolowik M, Peter Shih MT, Pillai SP, Cooper JA, Quaye EA . Quantitative evaluation of bacteria released by bathers in a marine water . Water Research . 41 . 1 . 3–10 . January 2007 . 17113123 . 2633726 . 10.1016/j.watres.2006.10.005 . 2007WatRe..41....3E .