Skip to main content
Log in

Clonality of epidemic methicillin-resistant Staphylococcus aureus strains in Finland as defined by several molecular methods

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

In Finland, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) strains has increased ten fold within the last decade. In order to follow the changing epidemiology of MRSA, accurate typing of S. aureus strains is important. The purpose of this study was to reanalyse 44 previously recognised Finnish epidemic MRSA strains (EMRSA) by several molecular typing methods and to revise their nomenclature. The 44 EMRSA strains were grouped into 26 pulsed-field gel electrophoresis (PFGE) clusters, 20 multi locus sequence typing (MLST) sequence types (ST) belonging to 12 clonal complexes (CC) of which CC8 was the most prevalent, and 27 spa types belonging to four clonal complexes. The staphylococcal cassette chromosome mec (SCCmec) type IV was predominant, and 48% of the strains were nonmultiresistant to antibiotics. The discriminatory power of PFGE clusters, MLST, and spa typing was high. The overall concordance values of typing methods differed when assessed by two different methods. Adjusted Rand coefficient provided fairly low correlations for all comparisons. However, spa type was able to efficiently predict types and clonal complexes of most of the other methods with high probability (≥80%).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Kerttula AM, Lyytikainen O, Salmenlinna S, Vuopio-Varkila J (2004) Changing epidemiology of methicillin-resistant Staphylococcus aureus in Finland. J Hosp Infect 58(2):109–114

    Article  PubMed  Google Scholar 

  2. Ibrahem S, Salmenlinna S, Kerttula AM, Virolainen-Julkunen A, Kuusela P, Vuopio-Varkila J (2005) Comparison of genotypes of methicillin-resistant and methicillin-sensitive Staphylococcus aureus in Finland. Eur J Clin Microbiol Infect Dis 24(5):325–328

    Article  PubMed  CAS  Google Scholar 

  3. Murchan S, Kaufmann ME, Deplano A, de Ryck R, Struelens M, Zinn CE, Fussing V, Salmenlinna S, Vuopio-Varkila J, El Solh N, Cuny C, Witte W, Tassios PT, Legakis N, van Leeuwen W, van Belkum A, Vindel A, Laconcha I, Garaizar J, Haeggman S, Olsson-Liljequist B, Ransjo U, Coombes G, Cookson B (2003) Harmonization of pulsed-field gel electrophoresis protocols for epidemiological typing of strains of methicillin-resistant Staphylococcus aureus: a single approach developed by consensus in 10 European laboratories and its application for tracing the spread of related strains. J Clin Microbiol 41(4):1574–1585

    Article  PubMed  CAS  Google Scholar 

  4. Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG (2000) Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol 38(3):1008–1015

    PubMed  CAS  Google Scholar 

  5. Oliveira DC, de Lencastre H (2002) Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 46(7):2155–2161

    Article  PubMed  CAS  Google Scholar 

  6. Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE, Bost DA, Riehman M, Naidich S, Kreiswirth BN (1999) Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol 37(11):3556–3563

    PubMed  CAS  Google Scholar 

  7. Tang YW, Waddington MG, Smith DH, Manahan JM, Kohner PC, Highsmith LM, Li H, Cockerill FR 3rd, Thompson RL, Montgomery SO, Persing DH (2000) Comparison of protein A gene sequencing with pulsed-field gel electrophoresis and epidemiologic data for molecular typing of methicillin-resistant Staphylococcus aureus. J Clin Microbiol 38(4):1347–1351

    PubMed  CAS  Google Scholar 

  8. Okuma K, Iwakawa K, Turnidge JD, Grubb WB, Bell JM, O’Brien FG, Coombs GW, Pearman JW, Tenover FC, Kapi M, Tiensasitorn C, Ito T, Hiramatsu K (2002) Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol 40(11):4289–4294

    Article  PubMed  CAS  Google Scholar 

  9. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminathan B (1995) Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33(9):2233–2239

    PubMed  CAS  Google Scholar 

  10. Pitcher DG, Saunders NA, Owen RJ (1989) Rapid extraction of bacterial genomic DNA with guanidium thiocyanate. Lett Appl Microbiol 8:151–156

    Article  CAS  Google Scholar 

  11. Struelens MJ, Deplano A, Godard C, Maes N, Serruys E (1992) Epidemiologic typing and delineation of genetic relatedness of methicillin-resistant Staphylococcus aureus by macrorestriction analysis of genomic DNA by using pulsed-field gel electrophoresis. J Clin Microbiol 30(10):2599–2605

    PubMed  CAS  Google Scholar 

  12. Crisostomo MI, Westh H, Tomasz A, Chung M, Oliveira DC, de Lencastre H (2001) The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones. Proc Natl Acad Sci USA 98(17):9865–9870

    Article  PubMed  CAS  Google Scholar 

  13. Aires-de-Sousa M, Boye K, de Lencastre H, Deplano A, Enright MC, Etienne J, Friedrich A, Harmsen D, Holmes A, Huijsdens XW, Kearns AM, Mellmann A, Meugnier H, Rasheed JK, Spalburg E, Strommenger B, Struelens MJ, Tenover FC, Thomas J, Vogel U, Westh H, Xu J, Witte W (2006) High interlaboratory reproducibility of DNA sequence-based typing of bacteria in a multicenter study. J Clin Microbiol 44(2):619–621

    Article  PubMed  CAS  Google Scholar 

  14. Strommenger B, Kettlitz C, Weniger T, Harmsen D, Friedrich AW, Witte W (2006) Assignment of Staphylococcus isolates to groups by spa typing, smaI macrorestriction analysis, and multilocus sequence typing. J Clin Microbiol 44(7):2533–2540

    Article  PubMed  CAS  Google Scholar 

  15. Harmsen D, Claus H, Witte W, Rothganger J, Turnwald D, Vogel U (2003) Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management. J Clin Microbiol 41(12):5442–5448

    Article  PubMed  CAS  Google Scholar 

  16. Kerttula AM, Lyytikainen O, Vuopio-Varkila J, Ibrahem S, Agthe N, Broas M, Jagerroos H, Virolainen A (2005) Molecular epidemiology of an outbreak caused by methicillin-resistant Staphylococcus aureus in a health care ward and associated nursing home. J Clin Microbiol 43(12):6161–6163

    Article  PubMed  CAS  Google Scholar 

  17. Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V, Vandenesch F, Etienne J (1999) Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 29(5):1128–1132

    Article  PubMed  CAS  Google Scholar 

  18. Brakstad OG, Aasbakk K, Maeland JA (1992) Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene. J Clin Microbiol 30(7):1654–1660

    PubMed  CAS  Google Scholar 

  19. Murakami K, Minamide W, Wada K, Nakamura E, Teraoka H, Watanabe S (1991) Identification of methicillin-resistant strains of staphylococci by polymerase chain reaction. J Clin Microbiol 29(10):2240–2244

    PubMed  CAS  Google Scholar 

  20. Hunter PR, Gaston MA (1988) Numerical index of the discriminatory ability of typing systems: an application of Simpson’s index of diversity. J Clin Microbiol 26(11):2465–2466

    PubMed  CAS  Google Scholar 

  21. Grundmann H, Hori S, Tanner G (2001) Determining confidence intervals when measuring genetic diversity and the discriminatory abilities of typing methods for microorganisms. J Clin Microbiol 39(11):4190–4192

    Article  PubMed  CAS  Google Scholar 

  22. Robinson DA, Hollingshead SK, Musser JM, Parkinson AJ, Briles DE, Crain MJ (1998) The IS1167 insertion sequence is a phylogenetically informative marker among isolates of serotype 6B Streptococcus pneumoniae. J Mol Evol 47(2):222–229

    Article  PubMed  CAS  Google Scholar 

  23. Hubert L, Arabie P (1985) Comparing partitions. J Classif 2:193–218

    Article  Google Scholar 

  24. Wallace DL (1983) A method for comparing two hierarchical clusterings: comment. J Am Stat Assoc 78:569–576

    Article  Google Scholar 

  25. Salmenlinna S, Lyytikainen O, Vuopio-Varkila J (2002) Community-acquired methicillin-resistant Staphylococcus aureus, Finland. Emerg Infect Dis 8(6):602–607

    PubMed  Google Scholar 

  26. Kerttula AM, Lyytikainen O, Karden-Lilja M, Ibrahem S, Salmenlinna S, Virolainen A, Vuopio-Varkila J (2007) Nationwide trends in molecular epidemiology of methicillin-resistant Staphylococcus aureus, Finland, 1997–2004. BMC Infect Dis 7(1):94. DOI 10.1186/1471-2334-1187-1194

    Article  PubMed  Google Scholar 

  27. Cookson BD, Robinson DA, Monk AB, Murchan S, Deplano A, de Ryck R, Struelens MJ, Scheel C, Fussing V, Salmenlinna S, Vuopio-Varkila J, Cuny C, Witte W, Tassios PT, Legakis NJ, van Leeuwen W, van Belkum A, Vindel A, Garaizar J, Haeggman S, Olsson-Liljequist B, Ransjo U, Muller-Premru M, Hryniewicz W, Rossney A, O’Connell B, Short BD, Thomas J, O’Hanlon S, Enright MC (2007) Evaluation of molecular typing methods in characterizing a European collection of epidemic methicillin-resistant Staphylococcus aureus strains: the HARMONY collection. J Clin Microbiol 45(6):1830–1837

    Article  PubMed  CAS  Google Scholar 

  28. Kotilainen P, Routamaa M, Peltonen R, Oksi J, Rintala E, Meurman O, Lehtonen OP, Eerola E, Salmenlinna S, Vuopio-Varkila J, Rossi T (2003) Elimination of epidemic methicillin-resistant Staphylococcus aureus from a university hospital and district institutions, Finland. Emerg Infect Dis 9(2):169–175

    PubMed  Google Scholar 

  29. Salmenlinna S, Lyytikainen O, Kotilainen P, Scotford R, Siren E, Vuopio-Varkila J (2000) Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Finland. Eur J Clin Microbiol Infect Dis 19(2):101–107

    Article  PubMed  CAS  Google Scholar 

  30. Karden-Lilja M, Ibrahem S, Vuopio-Varkila J, Salmenlinna S, Lyytikainen O, Siira L, Virolainen A (2007) Panton-Valentine leukocidin genes and staphylococcal chromosomal cassette mec types amongst Finnish community-acquired methicillin-resistant Staphylococcus aureus strains, 1997–1999. Eur J Clin Microbiol Infect Dis 26(10):729–733

    Article  PubMed  CAS  Google Scholar 

  31. Kotilainen P, Routamaa M, Peltonen R, Evesti P, Eerola E, Salmenlinna S, Vuopio-Varkila J, Rossi T (2001) Eradication of methicillin-resistant Staphylococcus aureus from a health center ward and associated nursing home. Arch Intern Med 161(6):859–863

    Article  PubMed  CAS  Google Scholar 

  32. Pastila S, Sammalkorpi KT, Vuopio-Varkila J, Kontiainen S, Ristola MA (2004) Control of methicillin-resistant Staphylococcus aureus outbreak involving several hospitals. J Hosp Infect 58(3):180–186

    Article  PubMed  CAS  Google Scholar 

  33. Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann H, Edwards G, O’Brien FG, Tenover FC, McDougal LK, Monk AB, Enright MC (2005) Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone. Lancet 365(9466):1256–1258

    Article  PubMed  Google Scholar 

  34. Robinson DA, Monk AB, Cooper JE, Feil EJ, Enright MC (2005) Evolutionary genetics of the accessory gene regulator (agr) locus in Staphylococcus aureus. J Bacteriol 187(24):8312–8321

    Article  PubMed  CAS  Google Scholar 

  35. Faria NA, Oliveira DC, Westh H, Monnet DL, Larsen AR, Skov R, de Lencastre H (2005) Epidemiology of emerging methicillin-resistant Staphylococcus aureus (MRSA) in Denmark: a nationwide study in a country with low prevalence of MRSA infection. J Clin Microbiol 43(4):1836–1842

    Article  PubMed  CAS  Google Scholar 

  36. Blanc DS, Struelens MJ, Deplano A, De Ryck R, Hauser PM, Petignat C, Francioli P (2001) Epidemiological validation of pulsed-field gel electrophoresis patterns for methicillin-resistant Staphylococcus aureus. J Clin Microbiol 39(10):3442–3445

    Article  PubMed  CAS  Google Scholar 

  37. Carrico JA, Silva-Costa C, Melo-Cristino J, Pinto FR, de Lencastre H, Almeida JS, Ramirez M (2006) Illustration of a common framework for relating multiple typing methods by application to macrolide-resistant Streptococcus pyogenes. J Clin Microbiol 44(7):2524–2532

    Article  PubMed  CAS  Google Scholar 

  38. Faria NA, Carrico JA, Oliveira DC, Ramirez M, de Lencastre H (2008) Analysis of typing methods for epidemiological surveillance of both methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains. J Clin Microbiol 46(1):136–144

    Article  PubMed  CAS  Google Scholar 

  39. Miragaia M, Carrico JA, Thomas JC, Couto I, Enright MC, de Lencastre H (2008) Comparison of molecular typing methods for characterization of Staphylococcus epidermidis: proposal for clone definition. J Clin Microbiol 46(1):118–129

    Article  PubMed  CAS  Google Scholar 

  40. Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG (2002) The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci USA 99(11):7687–7692

    Article  PubMed  CAS  Google Scholar 

  41. Malachowa N, Sabat A, Gniadkowski M, Krzyszton-Russjan J, Empel J, Miedzobrodzki J, Kosowska-Shick K, Appelbaum PC, Hryniewicz W (2005) Comparison of multiple-locus variable-number tandem-repeat analysis with pulsed-field gel electrophoresis, spa typing, and multilocus sequence typing for clonal characterization of Staphylococcus aureus isolates. J Clin Microbiol 43(7):3095–3100

    Article  PubMed  CAS  Google Scholar 

  42. Wisplinghoff H, Ewertz B, Wisplinghoff S, Stefanik D, Plum G, Perdreau-Remington F, Seifert H (2005) Molecular evolution of methicillin-resistant Staphylococcus aureus in the metropolitan area of Cologne, Germany, from 1984 to 1998. J Clin Microbiol 43(11):5445–5451

    Article  PubMed  CAS  Google Scholar 

  43. Ruppitsch W, Indra A, Stoger A, Mayer B, Stadlbauer S, Wewalka G, Allerberger F (2006) Classifying spa types in complexes improves interpretation of typing results for methicillin-resistant Staphylococcus aureus. J Clin Microbiol 44(7):2442–2448

    Article  PubMed  CAS  Google Scholar 

  44. Kuhn G, Francioli P, Blanc DS (2006) Evidence for clonal evolution among highly polymorphic genes in methicillin-resistant Staphylococcus aureus. J Bacteriol 188(1):169–178

    Article  PubMed  CAS  Google Scholar 

  45. Oliveira DC, Tomasz A, de Lencastre H (2001) The evolution of pandemic clones of methicillin-resistant Staphylococcus aureus: identification of two ancestral genetic backgrounds and the associated mec elements. Microb Drug Resist 7(4):349–361

    Article  PubMed  CAS  Google Scholar 

  46. Arakere G, Nadig S, Swedberg G, Macaden R, Amarnath SK, Raghunath D (2005) Genotyping of methicillin-resistant Staphylococcus aureus strains from two hospitals in Bangalore, South India. J Clin Microbiol 43(7):3198–3202

    Article  PubMed  CAS  Google Scholar 

  47. Aires de Sousa M, Bartzavali C, Spiliopoulou I, Sanches IS, Crisostomo MI, de Lencastre H (2003) Two international methicillin-resistant Staphylococcus aureus clones endemic in a university hospital in Patras, Greece. J Clin Microbiol 41(5):2027–2032

    Article  PubMed  CAS  Google Scholar 

  48. Mato R, Campanile F, Stefani S, Crisostomo MI, Santagati M, Sanches SI, de Lencastre H (2004) Clonal types and multidrug resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) recovered in Italy during the 1990s. Microb Drug Resist 10(2):106–113

    Article  PubMed  CAS  Google Scholar 

  49. Ito T, Katayama Y, Asada K, Mori N, Tsutsumimoto K, Tiensasitorn C, Hiramatsu K (2001) Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 45(5):1323–1336

    Article  PubMed  CAS  Google Scholar 

  50. Ito T, Katayama Y, Hiramatsu K (1999) Cloning and nucleotide sequence determination of the entire mec DNA of pre-methicillin-resistant Staphylococcus aureus N315. Antimicrob Agents Chemother 43(6):1449–1458

    PubMed  CAS  Google Scholar 

  51. Ito T, Ma XX, Takeuchi F, Okuma K, Yuzawa H, Hiramatsu K (2004) Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase, ccrC. Antimicrob Agents Chemother 48(7):2637–2651

    Article  PubMed  CAS  Google Scholar 

  52. Sanches IS, Ramirez M, Troni H, Abecassis M, Padua M, Tomasz A, de Lencastre H (1995) Evidence for the geographic spread of a methicillin-resistant Staphylococcus aureus clone between Portugal and Spain. J Clin Microbiol 33(5):1243–1246

    PubMed  CAS  Google Scholar 

  53. Hanssen AM, Fossum A, Mikalsen J, Halvorsen DS, Bukholm G, Sollid JU (2005) Dissemination of community-acquired methicillin-resistant Staphylococcus aureus clones in northern Norway: sequence types 8 and 80 predominate. J Clin Microbiol 43(5):2118–2124

    Article  PubMed  CAS  Google Scholar 

  54. Diep BA, Carleton HA, Chang RF, Sensabaugh GF, Perdreau-RemingtonF (2006) Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus. J Infect Dis 193(11):1495–1503

    Article  PubMed  CAS  Google Scholar 

  55. Aires de Sousa M, Sanches IS, Ferro ML, Vaz MJ, Saraiva Z, Tendeiro T, Serra J, de Lencastre H (1998) Intercontinental spread of a multidrug-resistant methicillin-resistant Staphylococcus aureus clone. J Clin Microbiol 36(9):2590–2596

    PubMed  CAS  Google Scholar 

  56. Vandenesch F, Naimi T, Enright MC, Lina G, Nimmo GR, Heffernan H, Liassine N, Bes M, Greenland T, Reverdy ME, Etienne J (2003) Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 9(8):978–984

    PubMed  Google Scholar 

  57. Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, Lin F, Lin J, Carleton HA, Mongodin EF, Sensabaugh GF, Perdreau-Remington F (2006) Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367(9512):731–739

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank Heidi Husu for her skilled technical assistance. This data was partly presented at the 16th European Congress of Clinical Microbiology and Infectious Diseases, April 2006, Nice, France, Poster no. 460. We declare that the experiments comply with the current laws of Finland.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Vainio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vainio, A., Kardén-Lilja, M., Ibrahem, S. et al. Clonality of epidemic methicillin-resistant Staphylococcus aureus strains in Finland as defined by several molecular methods. Eur J Clin Microbiol Infect Dis 27, 545–555 (2008). https://doi.org/10.1007/s10096-008-0470-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-008-0470-1

Keywords

Navigation