Skip to main content
SpringerLink
Log in

Postoperative Enterococcus faecalis endophthalmitis: virulence factors leading to poor visual outcome

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose Postoperative endophthalmitis caused by Enterococcus faecalis often results in poor visual outcome due to retinal destruction. We evaluated the virulence factors of Enterococcus faecalis clinical isolates and analyzed their relationship with retinal destruction and poor visual outcomes in postoperative bacterial endophthalmitis (PBE) following cataract surgery.

Study design

Retrospective.

Methods

E. faecalis isolates from nine acute-onset PBE cases were examined using pulsed-field gel electrophoresis of genomic DNA, plasmid isolation and pheromone response experiments. Virulence determinant genes, including cytolysin (cylA), aggregation substance (asa1), enterococcal surface protein (esp), gelatinase (gelE) and adhesin of collagen from enterococci (ace), were examined by polymerase chain reaction. Expression of cytolysin and secreted protease were also tested. Retinal findings observed during vitrectomy surgery and final visual acuities were compared to obtained microbiological data. Poor visual outcome was defined as final visual acuity of less than 0.1 (decimal).

Results

Although nine isolates were collected, two were identical. Out of the eight different isolates, three were positive for both expressions of cytolysin and secreted proteases. Plasmid DNAs were isolated from six of eight isolates, while pheromone response was observed in five isolates. The asa1, esp and ace genes were positive in six, five and eight of the isolates, respectively. Patients with retinal destruction exhibited significantly higher prevalence of secreted protease expression versus those without (P < 0.05), and retinal destruction was related to poor visual outcome (P < 0.05).

Conclusions

Our data suggest that enterococcal secreted proteases were correlated to retinal destruction, thereby fostering poor visual outcomes in eyes with enterococcal endophthalmitis.

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

Similar content being viewed by others

References

  1. Endophthalmitis Vitrectomy Study Group. Microbiologic factors and visual outcome in the endophthalmitis vitrectomy study. Am J Ophthalmol. 1996;122:830–46.

    Article  Google Scholar 

  2. Booth MC, Hatter KL, Miller D, Davis J, Kowalski R, Parke DW, et al. Molecular epidemiology of Staphylococcus aureus and Enterococcus faecalis in endophthalmitis. Infect Immun. 1998;66:356–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Suzuki T, Todokoro D, Kobayakawa S, Sotozono C, Eguchi S, Miyata K, et al. Postcataract endophthalmitis caused by Enterococcus faecalis. Nippon Ganka Gakkai Zasshi. 2014;118:22–7 (in Japanese).

    PubMed  Google Scholar 

  4. Kuriyan AE, Sridhar J, Flynn HW Jr, Smiddy WE, Albini TA, Berrocal AM, et al. Endophthalmitis caused by Enterococcus faecalis: clinical features, antibiotic sensitivities, and outcomes. Am J Ophthalmol. 2014;158:1018–23.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sadaka A, Durand ML, Gilmore MS. Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: host-microbe interactions in intraocular infection. Prog Retin Eye Res. 2012;31:316–31.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jett BD, Jensen HG, Nordquist RE, Gilmore MS. Contribution of the pAD1-encoded cytolysin to the severity of experimental Enterococcus faecalis endophthalmitis. Infect Immun. 1992;60:2445–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Engelbert M, Mylonakis E, Ausubel FM, Calderwood SB, Gilmore MS. Contribution of gelatinase, serine protease, and fsr to the pathogenesis of Enterococcus faecalis endophthalmitis. Infect Immun. 2004;72:3628–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Suzuki T, Wada T, Kozai S, Ike Y, Gilmore MS, Ohashi Y. Contribution of secreted proteases to the pathogenesis of postoperative Enterococcus faecalis endophthalmitis. J Cataract Refract Surg. 2008;34:1776–84.

    Article  PubMed  Google Scholar 

  9. Stevens SX, Jensen HG, Jett BD, Gilmore MS. A hemolysin-encoding plasmid contributes to bacterial virulence in experimental Enterococcus faecalis endophthalmitis. Invest Ophthalmol Vis Sci. 1992;33:1650–6.

    CAS  PubMed  Google Scholar 

  10. Mylonakis E, Engelbert M, Qin X, Sifri CD, Murray BE, Ausubel FM, et al. The Enterococcus faecalis fsrB gene, a key component of the fsr quorum-sensing system, is associated with virulence in the rabbit endophthalmitis model. Infect Immun. 2002;70:4678–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Garsin DA, Frank KL, Silanpaa J, Ausubel FM, Hartke A, Shankar N, et al. Pathogenesis and Models of Enterococcal Infection. In: Gilmore MS, Clewell DB, Ike Y, Shankar N, editors. Enterococci: from commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014.

    Google Scholar 

  12. Vankerckhoven V, Van Autgaerden T, Vael C, Lammens C, Chapelle S, Rossi R, et al. Development of a multiplex PCR for the detection of asa1, gelE, cylA, esp, and hyl genes in enterococci and survey for virulence determinants among European hospital isolates of Enterococcus faecium. J Clin Microbiol. 2004;42:4473–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tomita H, Ike Y. Tissue-specific adherent Enterococcus faecalis strains that show highly efficient adhesion to human bladder carcinoma T24 cells also adhere to extracellular matrix proteins. Infect Immun. 2004;72:5877–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Todokoro D, Tomita H, Inoue T, Ike Y. Genetic analysis of bacteriocin 43 of vancomycin-resistant Enterococcus faecium. Appl Environ Microbiol. 2006;72:6955–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ma X, Kudo M, Takahashi A, Tanimoto K, Ike Y. Evidence of nosocomial infection in Japan caused by high-level gentamicin-resistant Enterococcus faecalis and identification of the pheromone-responsive conjugative plasmid encoding gentamicin resistance. J Clin Microbiol. 1998;36:2460–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33:2233–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Fujimoto S, Clewell DB. Regulation of the pAD1 sex pheromone response of Enterococcus faecalis by direct interaction between the cAD1 peptide mating signal and the negatively regulating, DNA-binding TraA protein. Proc Natl Acad Sci USA. 1998;95:6430–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ike Y, Clewell DB. Genetic analysis of the pAD1 pheromone response in Streptococcus faecalis, using transposon Tn917 as an insertional mutagen. J Bacteriol. 1984;158:777–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Huycke MM, Spiegel CA, Gilmore MS. Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis. Antimicrob Agents Chemother. 1991;35:1626–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Qin X, Singh KV, Weinstock GM, Murray BE. Effects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect Immun. 2000;68:2579–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yanai H. Statcel - The useful add-in software forms on Excel. 3rd ed. Tokyo: OMS; 2011.

    Google Scholar 

  22. Higashide T, Takahashi M, Kobayashi A, Ohkubo S, Sakurai M, Shirao Y, et al. Endophthalmitis caused by Enterococcus mundtii. J Clin Microbiol. 2005;43:1475–6.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jett BD, Huycke MM, Gilmore MS. Virulence of enterococci. Clin Microbiol Rev. 1994;7:462–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pescosolido N, Barbato A, Pascarella A, Giannotti R, Genzano M, Nebbioso M. Role of Protease-Inhibitors in Ocular Diseases. Molecules. 2014;19:20557–69.

    Article  PubMed  Google Scholar 

  25. Nakayama J, Yokohata R, Sato M, Suzuki T, Matsufuji T, Nishiguchi K, et al. Development of a peptide antagonist against fsr quorum sensing of Enterococcus faecalis. ACS Chem Biol. 2013;8:804–11.

    Article  CAS  PubMed  Google Scholar 

  26. Clewell DB, Weaver KE, Dunny GM, Coque TM, Francia MV, Hayes F. Extrachromosomal and mobile elements in Enterococci: transmission, maintenance, and epidemiology. In: Gilmore MS, Clewell DB, Ike Y, Shankar N, editors. Enterococci: from commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014.

    Google Scholar 

  27. Olmsted SB, Dunny GM, Erlandsen SL, Wells CL. A plasmid-encoded surface protein on Enterococcus faecalis augments its internalization by cultured intestinal epithelial cells. J Infect Dis. 1994;170:1549–56.

    Article  CAS  PubMed  Google Scholar 

  28. Jett BD, Atkuri RV, Gilmore MS. Enterococcus faecalis localization in experimental endophthalmitis: role of plasmid-encoded aggregation substance. Infect Immun. 1998;66:843–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Shankar N, Lockatell CV, Baghdayan AS, Drachenberg C, Gilmore MS, Johnson DE. Role of Enterococcus faecalis surface protein Esp in the pathogenesis of ascending urinary tract infection. Infect Immun. 2001;69:4366–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Toledo-Arana A, Valle J, Solano C, Arrizubieta MJ, Cucarella C, Lamata M, et al. The enterococcal surface protein, Esp, is involved in Enterococcus faecalis biofilm formation. Appl Environ Microbiol. 2001;67:4538–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Shankar V, Baghdayan AS, Huycke MM, Lindahl G, Gilmore MS. Infection-derived Enterococcus faecalis strains are enriched in esp, a gene encoding a novel surface protein. Infect Immun. 1999;67:193–200.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Okajima Y, Kobayakawa S, Iino N, Yanagawa H, Tochikubo T. Scanning electron microscope of endophthalmitis case. Nippon Ganka Gakkai Zasshi. 2005; 110: 44-50. [Japanese]

    Google Scholar 

Download references

Acknowledgements

We gratefully thank the Enterococci Endophthalmitis Working Group for providing data from a nationwide survey and Yasuyoshi Ike for his helpful discussions.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Daisuke Todokoro & Hideo Akiyama

  2. Ishizuchi Eye Clinic, Niihama, Ehime, Japan

    Takashi Suzuki

  3. Department of Ophthalmology, Nippon Medical School Tama Nagayama Hospital, Tama, Tokyo, Japan

    Shinichiro Kobayakawa

  4. Department of Bacteriology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Haruyoshi Tomita

  5. Laboratory of Bacterial Drug Resistance, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Haruyoshi Tomita

  6. Department of Ophthalmology, Ehime University School of Medicine, Toon, Ehime, Japan

    Yuichi Ohashi

Authors
  1. Daisuke Todokoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shinichiro Kobayakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haruyoshi Tomita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuichi Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideo Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daisuke Todokoro.

Ethics declarations

Conflicts of interest

D Todokoro, None; T. Suzuki, None; S. Kobayakawa, None; H. Tomita, None; Y. Ohashi, None; H. Akiyama, None.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Todokoro, D., Suzuki, T., Kobayakawa, S. et al. Postoperative Enterococcus faecalis endophthalmitis: virulence factors leading to poor visual outcome. Jpn J Ophthalmol 61, 408–414 (2017). https://doi.org/10.1007/s10384-017-0527-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-017-0527-8

Keywords

Search

Navigation