S. epidermidis : how to turn from commensal to be a pathogen lifestyle


Titik Nuryastuti(1*)

(1) Department of Microbiology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author


Staphylococcus epidermidis normally is a commensal inhabitant of healthy human skin and mucosa, but also a common nosocomial pathogen in immunocompromised patients, neonates, and patients with indwelling medical devices. To distinguish the pathogen and commensal strain is a big challenge when identifying this agent with its related infection. This mini-review aims to summarize recent research in this area with a special emphasis on the virulence factor of generating genotypic and phenotypic diversity in S. epidermidis.

By living between a commensal and pathogen, S. epidermidis needed to establish many strategies to face different clinical environments, including the new ecological niche of biomaterials. In addition, the growing number of immunocompromised patients increased the risk for a very sensitive host. However, further exploration of the relationship between virulence factor and in vivo pathogenesis is still needed. According to the virulence factor of these bacteria, which are considered as a real pathogen, strict control measures should be taken for S. epidermidis infection.


Staphylococcus epidermidis; commensal; pathogen; virulence factor; biofilm

Full Text:



Becker K, Heilmann C, Peters G. Coagulase-Negative Staphylococci. Clin Microbiol Rev. 2014;27(4):870–926. http://doi:10.1128/CMR.00109-13 2. Christensen GJM, Brüggemann H. Bacterial skin commensals and their role as host guardians. Benef Microbes. 2014;5(2):201–15. http://doi:10.3920/BM2012.0062 3. Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2013;9(4):244–53. http://doi:10.1038/nrmicro2537 4. Otto M. Staphylococcus epidermidis-the’accidental’pathogen. Nat Rev Microbiol 2009;7(8):555–67. http://doi:10.1038/nrmicro2182 5. Vuong C, Otto M. Staphylococcus epidermidis infections. Microbes Infect. 2002;4(4):481–9. http://doi:10.1016/S1286-4579(02)01563-0 6. Cerca N, Pier GB, Vilanova M, Oliveira R, Azeredo J. Quantitative analysis of adhesion and biofilm formation on hydrophilic and hydrophobic surfaces of clinical isolates of Staphylococcus epidermidis. Res Microbiol. 2005;156:506–514. http://doi:10.1016/j.resmic.2005.01.007 7. Gomes F, Teixeira P, Oliveira R. Mini-review : Staphylococcus epidermidis as the most frequent cause of nosocomial infections : old and new fighting strategies. Biofouling. 2014;30(2):131-41. http://doi:10.1080/08927014.2013.848858 8. Ziebuhr W, Hennig S, Eckart M, Kr H, Batzilla C, Kozitskaya S. Nosocomial infections by Staphylococcus epidermidis: how a commensal bacterium turns into a pathogen. Int J Antimicrob Agents. 2006;28S:S14–20. http://doi:10.1016/j.ijantimicag.2006.05.012 9. Garrett TR, Bhakoo M, Zhang Z. Bacterial adhesion and biofilms on surfaces. Prog Nat Sci. 2008;18(9):1049–56. http://doi:10.1016/j.pnsc.2008.04.001 10. Brescó MS, Harris LG, Thompson K, Stanic B, Morgenstern M, Mahony LO, et al. Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis device-related infection. Front Microbiol. 2017;8(1401). http://doi:10.3389/fmicb.2017.01401 11. O’Gara JP. ica and beyond: Biofilm mechanisms and regulation in Staphylococcus epidermidis and Staphylococcus aureus. FEMS Microbiol Lett. 2007;270(2):179–88. http://doi:10.1111/j.1574-6968.2007.00688 12. Suja KRS, Sheela P, Jyothis S, Radhakrishnan EK. Virulence factors associated with Coagulase Negative Staphylococci isolated from human infections. 3 Biotech. 2017;7(140):1–10. http://doi:10.1007/s13205-017-0753-2 13. Mack D, Davies AP, Harris LG, Jeeves R, Pascoe B, Knobloch JK, et al. Staphylococcus epidermidis in Biomaterial-Associated Infections. In: T.F. Moriarty et al., editor, Biomaterials Associated Infection: Immunological Aspects and Antimicrobial Strategies. New York: Springer Science Business Media; 2013. p 25-57. http://doi:10.1007/978-1-4614-1031-7 14. Lewis Kim. Minireview Riddle of Biofilm Resistance. Antimicrob Agents Chemother. 2001;45(4):999–1007. http://doi:10.1128/AAC.45.4.999 15. Prasad S, Nayak N, Satpathy G, Nag HL, Venkatesh P, Ramakrishnan S. Molecular & phenotypic characterization of Staphylococcus epidermidis in implant related infections. Indian J Med Res. 2012;136:483–90. 16. de la Fuente-Nunez C, Reffuveille F, Fernandez L, Hancock REW. Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies. Curr Opin Microbiol. 2013;580–9. http://doi:10.1016/j.mib.2013.06.013 17. Wilkins M, Hall-stoodley L, Allan RN, Faust SN. New approaches to the treatment of biofilm-related infections. J Infect. 2014;69:S47–52. http://doi:10.1016/j.jinf.2014.07.014 18. Lindsay D, von Holy A. Bacterial biofilms within the clinical setting : what healthcare professionals should know. J Hosp Infect. 2006;64:313-25 http://doi:10.1016/j.jhin.2006.06.028 19. Mack D, Davies AP, Harris LG, Jeeves R, Pascoe B, Knobloch JKM, et al. Staphylococcus epidermidis in biomaterial-associated infections. In: T.F. Moriarty et al., editor, Biomaterials Associated Infection: Immunological Aspects and Antimicrobial Strategies. New York: Springer Science Business Media; 2013. p 25-57 http://doi:10.1007/978-1-4614-1031-7_2 20. Schoenfelder SMK, Lange C, Eckart M, Hennig S, Kozytska S, Ziebuhr W. International Journal of Medical Microbiology Success through diversity – How Staphylococcus epidermidis establishes as a nosocomial pathogen. Int J Med Microbiol. 2010;300(6):380–6. http://doi:10.1016/j.ijmm.2010.04.011 21. Kozitskaya S, Olson ME, Fey PD, Witte W, Ohlsen K, Ziebuhr W, et al. Clonal analysis of Staphylococcus epidermidis isolates carrying or lacking biofilm-mediating genes by multilocus sequence typing. J Clin Microbiol. 2005;43(9):4751–7. http://doi:10.1128/JCM.43.9.4751 22. Bryers JD. Medical Biofilms. Biotechnol Bioeng. 2009;100(1):1–18. http://doi:10.1002/bit.21838 23. Nuryastuti T. Environmental signals affecting ica-expression in Staphylococcus epidermidis biofilms. [Dissertation]. The Netherlands: University of Groningen; 2010. 24. Bos R, Mei HC Van Der, Busscher HJ. Physico-chemistry of initial microbial adhesive interactions-its mechanisms and methods for study. FEMS Microbiol Rev. 1999;23:179-230. 25. von Eiff C, Peters G, Heilmann C. Pathogenesis of infections due to coagulase negative staphylococci. Lancet Infect Dis. 2002;2(11):677–85. http://doi:10.1016/S1473-3099(02)00438-3 26. Rohde H, Frankenberger S, Zähringer U, Mack D. Structure, function and contribution of polysaccharide intercellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biomaterial-associated infections. Eur J Cell Biol. 2010;89(1):103–11. http://doi:10.1016/j.ejcb.2009.10.005 27. Cramton SE, Gerke C, Schnell NF, Nichols WW, Gotz F. The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun. 1999;67(10):5427–33. 28. Nuryastuti T, van der Mei HC, Busscher HJ, Kuijer R, Aman AT, Krom BP. recA mediated spontaneous deletions of the icaADBC operon of clinical Staphylococcus epidermidis isolates: A new mechanism of phenotypic variations. Antonie van Leeuwenhoek, Int J Gen Mol Microbiol. 2008;94(2):317–28. http://doi:10.1007/s10482-008-9249-8 29. Arciola CR, Campoccia D, Ravaioli S, Montanaro L. Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects. Front Cell Infect Microbiol. 2015;5(7):1-10. http://doi:10.3389/fcimb.2015.00007 30. Knobloch JK, Horstkotte MA, Rohde H, Kaulfers P. Alcoholic ingredients in skin disinfectants increase biofilm expression of Staphylococcus epidermidis. J Antimicrobial Chemother. 2002;49:683–7. 31. Cramton SE, Ulrich M, Gotz F, Doring G. Anaerobic conditions induce expression of polysaccharide intercellular adhesin in Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun. 2001;69(6):4079–85. http://doi:10.1128/IAI.69.6.4079 32. Rachid S, Ohlsen K, Witte W, Hacker RG, Ziebuhr W. Effect of subinhibitory antibiotic concentrations on polysaccharide intercellular adhesin expression in biofilm-forming Staphylococcus epidermidis. Antimicrob Agents Chemother. 2000;44(12):3357–63. 33. Fitzpatrick F, Humphreys H, O’Gara JP. The genetics of staphylococcal biofilm formation-will a greater understanding of pathogenesis lead to better management of device-related infection? Eur Soc Clin Infect Dis. 2005;11(12):967–73. http://doi:10.1111/j.1469-0691.2005.01274.x 34. Li H, Xu L, Wang J, Wen Y, Vuong C, Otto M, et al. Conversion of Staphylococcus epidermidis strains from commensal to invasive by expression of the ica locus encoding production of biofilm exopolysaccharide. Infect Immun. 2005;73(5):3188–91. http://doi:10.1128/IAI.73.5.3188 35. O’Gara JP, Humphreys H. Staphylococcus epidermidis biofilms: importance and implications. J Med Microbiol. 2001;50:582–7. http://doi:10.1099/0022-1317-50-7-582 36. Rohde H, Frankenberger S, Zähringer U, Mack D. Structure, function and contribution of polysaccharide intercellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biomaterial-associated infections. Eur J Cell Biol. 2010;89(1):103–11. http://doi:10.1016/j.ejcb.2009.10.005 37. Vandecasteele SJ, Peetermans WE, Merckx RR, Rijnders BJA, van Eldere J. Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections. Eur Soc Clin Infect Dis. 2003;9(2):114–9. http://doi:10.1046/j.1469-0691.2003.00544 38. Chessa D, Ganau G, Spiga L, Bulla A, Mazzarello V. Staphylococcus aureus and Staphylococcus epidermidis virulence strains as causative agents of persistent infections in breast implants. PLoS ONE. 2016;11(1): e0146668. http://doi:10.1371/journal.pone.0146668 39. Cafiso V, Bertuccio T, Santagati M, Campanile F, Amicosante G, Perilli MG, et al. Presence of the ica operon in clinical isolates of Staphylococcus epidermidis and its role in biofilm production. Clin Microbiol Infect. 2004;10(12):1081–8. http://doi:10.1111/j.1469-0691.2004.01024 40. Nuryastuti T, Mei HC Van Der, Busscher HJ, Kuijer R, Aman AT, Krom BP. High frequency spontaneous deletions within the icaADBC operon of clinical Staphylococcus epidermidis Isolates. IJBiotech. 2012;17(2):144–53. 41. Kozitskaya S, Cho S, Dietrich K, Marre R, Naber K, Ziebuhr W. The bacterial insertion sequence element IS 256 occurs preferentially in nosocomial Staphylococcus epidermidis Isolates : association with biofilm formation and resistance to aminoglycosides. Infect Immun. 2004;72(2):1210–5. http://doi:10.1128/IAI.72.2.1210 42. Hennig S, Ziebuhr W. A transposase-independent mechanism gives rise to precise excision of IS 256 from insertion sites in Staphylococcus epidermidis. J Bacteriol. 2008;190(4):1488–90. http://doi:10.1128/JB.01290-07 43. Bogut A, Niedz J, Kozioł-Montewka M, Strzelec-Nowak D, Blacha J, Mazurkiewicz T, et al. Characterization of Staphylococcus epidermidis and Staphyloccocus warneri small-colony variants associated with prosthetic-joint infections. J Med Microbiol. 2014;63:176–85. http://doi:10.1099/jmm.0.066068-0 44. Eiff C Von, Vaudaux P, Kahl BC, Lew D, Emler S, Schmidt A, et al. Bloodstream Infections caused by small-colony variants of coagulase-negative staphylococci following pacemaker implantation. Clin Infect Dis. 1999;29:932–4. 45. Tande AJ, Osmon DR, Greenwood-quaintance KE, Mabry TM, Hanssen AD. Clinical characteristics and outcomes of prosthetic joint infection caused by small colony variant staphylococci. mBio. 2014;5(5):e01910-14. http://doi:10.1128/mBio.01910-14 46. Laham N Al. Mini-review: Formation, antibiotic resistance and clinical outcome of infections associated with small colony variants of staphylococci. In: Méndez-Vilas A, editor, Microbial pathogens and strategies for combating them: science, technology and education. Formatex; 2013. p 497–507. 47. Laham N Al, Rohde H, Sander G, Fischer A, Hussain M, Heilmann C, et al. Augmented expression of polysaccharide intercellular adhesin in a defined Staphylococcus epidermidis mutant with the small-colony-variant phenotype. J Bacteriol. 2007;189(12):4494–501. http://doi:10.1128/JB.00160-07 48. von Eiff C, Reinert RR, Kresken M, Brauers J, Hafner D, Peters G, et al. Nationwide German multicenter study on prevalence of antibiotic resistance in staphylococcal bloodstream isolates and comparative in vitro activities of quinupristin-dalfopristin. J Clin Microbiol. 2000;38(8):2819–23. 49. Seng R, Leungtongkam U, Thummeepak R, Chatdumrong W, Sitthisak S. High prevalence of methicillin-resistant coagulase-negative staphylococci isolated from a university environment in Thailand. Int Microbiol. 2017;20(2):65–73. http://doi:10.2436/20.1501.01.286 50. Watanabe S, Ohnishi T, Yuasa A, Kiyota H, Shimizu T, Hatta N, et al. The first nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan. J Infect Chemother. 2017;23(8):503–11. http://doi:10.1016/j.jiac.2017.05.006 51. Li M, Wang X, Gao Q, Lu Y, Lu Y. Molecular characterization of Staphylococcus epidermidis strains isolated from a teaching hospital in Shanghai, China. J Med Microbiol. 2009;58:456–61. http://doi:10.1099/jmm.0.007567-0 52. Kristóf K, Pongrácz J. Interpretation of blood microbiology results – function of the clinical microbiologist. J Int Fed Clin Chem Lab Med. 2016;27(2):147–55. 53. Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013;56(1):e1–25. http://doi:10.1093/cid/cis803 54. Baron EJ. The role of the clinical microbiology laboratory in the diagnosis of selected infectious processes. J Clin Microbiol. 2011;49(9Suppl):S25 http://doi:10.1128/JCM.00842-11 55. Acker H Van, Dijck P Van, Coenye T. Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms. Trends Microbiol. 2014;22(6):326–33. http://doi:10.1016/j.tim.2014.02.001

DOI: https://doi.org/10.19106/JMedSci005001201813

Article Metrics

Abstract views : 4299 | views : 3610

Copyright (c) 2018 Titik Nuryastuti

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

View My Stats


Creative Commons License
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.