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Volume 159, Issue Pt_8

Large mobile genetic elements carrying resistance genes that do not confer a fitness burden in healthcare-associated meticillin-resistant Free

Abstract

Healthcare-associated (HA) meticillin-resistant (MRSA) clone CC22 SCCIV (EMRSA-15) has recently overtaken CC30/ST36 SCCII (EMRSA-16) as the dominant clone in UK hospitals. CC22 SCCIV shows greater fitness than CC30 SCCII, although both are successful global pathogens. The aim of this study was to test whether mobile genetic elements (MGEs), specifically SCC and large plasmids encoding resistance genes, are a burden and contribute to this fitness difference. Thirty-nine clinical isolates of MRSA and meticillin-sensitive from lineages CC30 and CC22 with a variety of antibiotic resistance genes were grown in the absence of antibiotics. A range of relative fitness measures were used to compare clinical isolates with and without SCCII and SCCIV. The same fitness measures were used to compare eight isolates with and without naturally occurring large antibiotic resistance plasmids carrying gentamicin resistance (determined by microarray) and an isolate with an introduced plasmid. Growth rate, competitive ability during co-culture and survival after desiccation were then compared. Carriage of SCCII contributed to the reduced fitness of CC30 MRSA. However, we found no evidence of a fitness cost due to carriage of SCCIV in CC22, or large antibiotic resistance plasmids in CC30 or multiple resistances in both lineages. In conclusion, many large MGEs are not a fitness burden. Surprisingly, lineage background was the most important determinant of fitness. Our results suggest CC22 SCCIV will remain a successful healthcare-associated clone, and resistance to meticillin and gentamicin is likely to be maintained even in the absence of antibiotic pressure.

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2013-08-01
2024-04-16
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References

  1. Andersson D. I., Hughes D. ( 2010). Antibiotic resistance and its cost: is it possible to reverse resistance?. Nat Rev Microbiol 8:260–271[PubMed]
     [Google Scholar]
  2. Bastos M. C., Mondino P. J., Azevedo M. L., Santos K. R., Giambiagi-deMarval M. ( 1999). Molecular characterization and transfer among Staphylococcus strains of a plasmid conferring high-level resistance to mupirocin. Eur J Clin Microbiol Infect Dis 18:393–398 [View Article][PubMed]
     [Google Scholar]
  3. Bergstrom C. T., Lo M., Lipsitch M. ( 2004). Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals. Proc Natl Acad Sci U S A 101:13285–13290 [View Article][PubMed]
     [Google Scholar]
  4. Bertrand X., Thouverez M., Talon D. ( 2000). Antibiotic susceptibility and genotypic characterization of methicillin-resistant Staphylococcus aureus strains in eastern France. J Hosp Infect 46:280–287 [View Article][PubMed]
     [Google Scholar]
  5. Björkman J., Andersson D. I. ( 2000). The cost of antibiotic resistance from a bacterial perspective. Drug Resist Updat 3:237–245 [View Article][PubMed]
     [Google Scholar]
  6. Bouma J. E., Lenski R. E. ( 1988). Evolution of a bacteria/plasmid association. Nature 335:351–352 [View Article][PubMed]
     [Google Scholar]
  7. Clewell D. B., An F. Y., White B. A., Gawron-Burke C. ( 1985). Streptococcus faecalis sex pheromone (cAM373) also produced by Staphylococcus aureus and identification of a conjugative transposon (Tn918). J Bacteriol 162:1212–1220[PubMed]
     [Google Scholar]
  8. Cockfield J. D., Pathak S., Edgeworth J. D., Lindsay J. A. ( 2007). Rapid determination of hospital-acquired meticillin-resistant Staphylococcus aureus lineages. J Med Microbiol 56:614–619 [View Article][PubMed]
     [Google Scholar]
  9. Collins J., Rudkin J., Recker M., Pozzi C., O’Gara J. P., Massey R. C. ( 2010). Offsetting virulence and antibiotic resistance costs by MRSA. ISME J 4:577–584 [View Article][PubMed]
     [Google Scholar]
  10. D’Agata E. M. C., Horn M., Webb G. ( 2007). Quantifying the impact of bacterial fitness and repeated antimicrobial exposure on the emergence of multidrug-resistant gram-negative bacilli. Math Model Nat Phenom 2:129–142 [View Article]
     [Google Scholar]
  11. Dahlberg C., Chao L. ( 2003). Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12. Genetics 165:1641–1649[PubMed]
     [Google Scholar]
  12. DeLeo F. R., Otto M., Kreiswirth B. N., Chambers H. F. ( 2010). Community-associated meticillin-resistant Staphylococcus aureus . Lancet 375:1557–1568 [View Article][PubMed]
     [Google Scholar]
  13. Deurenberg R. H., Stobberingh E. E. ( 2008). The evolution of Staphylococcus aureus. . Infect Genet Evol 8:747–763 [View Article][PubMed]
     [Google Scholar]
  14. Diep B. A., Stone G. G., Basuino L., Graber C. J., Miller A., des Etages S. A., Jones A., Palazzolo-Ballance A. M., Perdreau-Remington F. & other authors ( 2008). The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus. . J Infect Dis 197:1523–1530 [View Article][PubMed]
     [Google Scholar]
  15. Ender M., McCallum N., Adhikari R., Berger-Bächi B. ( 2004). Fitness cost of SCCmec and methicillin resistance levels in Staphylococcus aureus. . Antimicrob Agents Chemother 48:2295–2297 [View Article][PubMed]
     [Google Scholar]
  16. Enright M. C., Day N. P., Davies C. E., Peacock S. J., Spratt B. G. ( 2000). Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus . J Clin Microbiol 38:1008–1015[PubMed]
     [Google Scholar]
  17. Gemmell C. G., Edwards D. I., Fraise A. P., Gould F. K., Ridgway G. L., Warren R. E. Joint Working Party of the British Society for Antimicrobial Chemotherapy, Hospital Infection Society and Infection Control Nurses Association ( 2006). Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK. J Antimicrob Chemother 57:589–608 [View Article][PubMed]
     [Google Scholar]
  18. Godwin D., Slater J. H. ( 1979). The influence of the growth environment on the stability of a drug resistance plasmid in Escherichia coli K12. J Gen Microbiol 111:201–210 [View Article][PubMed]
     [Google Scholar]
  19. Grundmann H., Aanensen D. M., van den Wijngaard C. C., Spratt B. G., Harmsen D., Friedrich A. W. European Staphylococcal Reference Laboratory Working Group ( 2010). Geographic distribution of Staphylococcus aureus causing invasive infections in Europe: a molecular–epidemiological analysis. PLoS Med 7:e1000215 [View Article][PubMed]
     [Google Scholar]
  20. Helling R. B., Kinney T., Adams J. ( 1981). The maintenance of plasmid-containing organisms in populations of Escherichia coli . J Gen Microbiol 123:129–141[PubMed]
     [Google Scholar]
  21. Holden M. T., Feil E. J., Lindsay J. A., Peacock S. J., Day N. P., Enright M. C., Foster T. J., Moore C. E., Hurst L. & other authors ( 2004). Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc Natl Acad Sci U S A 101:9786–9791 [View Article][PubMed]
     [Google Scholar]
  22. 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 45:1323–1336 [View Article][PubMed]
     [Google Scholar]
  23. Jensen S. O., Apisiridej S., Kwong S. M., Yang Y. H., Skurray R. A., Firth N. ( 2010). Analysis of the prototypical Staphylococcus aureus multiresistance plasmid pSK1. Plasmid 64:135–142 [View Article][PubMed]
     [Google Scholar]
  24. Kluytmans J., van Belkum A., Verbrugh H. ( 1997). Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 10:505–520[PubMed]
     [Google Scholar]
  25. Knight G. M., Budd E. L., Whitney L., Thornley A., Al-Ghusein H., Planche T., Lindsay J. A. ( 2012). Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time. J Antimicrob Chemother 67:2514–2522 [View Article][PubMed]
     [Google Scholar]
  26. Kobayashi N., Wu H., Kojima K., Taniguchi K., Urasawa S., Uehara N., Omizu Y., Kishi Y., Yagihashi A., Kurokawa I. ( 1994). Detection of mecA, femA, and femB genes in clinical strains of staphylococci using polymerase chain reaction. Epidemiol Infect 113:259–266 [View Article][PubMed]
     [Google Scholar]
  27. Krebes J., Al-Ghusein H., Feasey N., Breathnach A., Lindsay J. A. ( 2011). Are nasal carriers of Staphylococcus aureus more likely to become colonized or infected with methicillin-resistant Staphylococcus aureus on admission to a hospital?. J Clin Microbiol 49:430–432 [View Article][PubMed]
     [Google Scholar]
  28. Kuroda M., Ohta T., Uchiyama I., Baba T., Yuzawa H., Kobayashi I., Cui L., Oguchi A., Aoki K. & other authors ( 2001). Whole genome sequencing of meticillin-resistant Staphylococcus aureus . Lancet 357:1225–1240 [View Article][PubMed]
     [Google Scholar]
  29. Kyslik P., Dobisova M., Maresova H., Sobotkova L. ( 1993). Plasmid burden in chemostat culture of Escherichia coli: its effect on the selection for overproducers of host enzymes. Biotechnol Bioeng 41:325–329 [View Article][PubMed]
     [Google Scholar]
  30. Laurent F., Lelièvre H., Cornu M., Vandenesch F., Carret G., Etienne J., Flandrois J.-P. ( 2001). Fitness and competitive growth advantage of new gentamicin-susceptible MRSA clones spreading in French hospitals. J Antimicrob Chemother 47:277–283 [View Article][PubMed]
     [Google Scholar]
  31. Lenski R. E., Bouma J. E. ( 1987). Effects of segregation and selection on instability of plasmid pACYC184 in Escherichia coli B. J Bacteriol 169:5314–5316[PubMed]
     [Google Scholar]
  32. Lenski R. E., Simpson S. C., Nguyen T. T. ( 1994). Genetic analysis of a plasmid-encoded, host genotype-specific enhancement of bacterial fitness. J Bacteriol 176:3140–3147[PubMed]
     [Google Scholar]
  33. Levin B. R., Rozen D. E. ( 2006). Non-inherited antibiotic resistance. Nat Rev Microbiol 4:556–562 [View Article][PubMed]
     [Google Scholar]
  34. Lindsay J. ( 2008). S. aureus Evolution: Lineages and Mobile Genetic Elements (MGEs). In Staphylococcus: Molecular Genetics45–69 Lindsay J. A. Norfolk, UK: Caister Academic Press;
     [Google Scholar]
  35. Lindsay J. A. ( 2010). Genomic variation and evolution of Staphylococcus aureus . Int J Med Microbiol 300:98–103 [View Article][PubMed]
     [Google Scholar]
  36. Lindsay J. A., Foster S. J. ( 1999). Interactive regulatory pathways control virulence determinant production and stability in response to environmental conditions in Staphylococcus aureus . Mol Gen Genet 262:323–331 [View Article][PubMed]
     [Google Scholar]
  37. Lindsay J. A., Ruzin A., Ross H. F., Kurepina N., Novick R. P. ( 1998). The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus . Mol Microbiol 29:527–543 [View Article][PubMed]
     [Google Scholar]
  38. Lyon B. R., Skurray R. ( 1987). Antimicrobial resistance of Staphylococcus aureus: genetic basis. Microbiol Rev 51:88–134[PubMed]
     [Google Scholar]
  39. Maisnier-Patin S., Andersson D. I. ( 2004). Adaptation to the deleterious effects of antimicrobial drug resistance mutations by compensatory evolution. Res Microbiol 155:360–369 [View Article][PubMed]
     [Google Scholar]
  40. McCarthy A. J., Lindsay J. A. ( 2010). Genetic variation in Staphylococcus aureus surface and immune evasion genes is lineage associated: implications for vaccine design and host–pathogen interactions. BMC Microbiol 10:173 [View Article][PubMed]
     [Google Scholar]
  41. McCarthy A. J., Lindsay J. A. ( 2012). The distribution of plasmids that carry virulence and resistance genes in Staphylococcus aureus is lineage associated. BMC Microbiol 12:104 [View Article][PubMed]
     [Google Scholar]
  42. McCarthy A. J., Breathnach A. S., Lindsay J. A. ( 2012). Detection of mobile genetic element (MGE) variation between colonising and infecting hospital-associated (HA)-MRSA isolates. J Clin Microbiol 50:1073–1075 [View Article][PubMed]
     [Google Scholar]
  43. McDermott P. J., Gowland P., Gowland P. C. ( 1993). Adaptation of Escherichia coli growth rates to the presence of pBR322. Lett Appl Microbiol 17:139–143 [View Article][PubMed]
     [Google Scholar]
  44. McDougal L. K., Steward C. D., Killgore G. E., Chaitram J. M., McAllister S. K., Tenover F. C. ( 2003). Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol 41:5113–5120 [View Article][PubMed]
     [Google Scholar]
  45. Modi R. I., Adams J. ( 1991). Coevolution in bacterial–plasmid populations. Evolution 45:656–667 [View Article]
     [Google Scholar]
  46. Mongkolrattanothai K., Pumfrey L., Mankin P., Gray B. M. ( 2009). Acquisition of high-level mupirocin resistance and its fitness cost among methicillin-resistant Staphylococcus aureus strains with low-level mupirocin resistance. J Clin Microbiol 47:4158–4160 [View Article][PubMed]
     [Google Scholar]
  47. Nielsen K. L., Pedersen T. M., Udekwu K. I., Petersen A., Skov R. L., Hansen L. H., Hughes D., Frimodt-Møller N. ( 2012). Fitness cost: a bacteriological explanation for the demise of the first international methicillin-resistant Staphylococcus aureus epidemic. J Antimicrob Chemother 67:1325–1332 [View Article][PubMed]
     [Google Scholar]
  48. Okuma K., Iwakawa K., Turnidge J. D., Grubb W. B., Bell J. M., O’Brien F. G., Coombs G. W., Pearman J. W., Tenover F. C. & other authors ( 2002). Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol 40:4289–4294 [View Article][PubMed]
     [Google Scholar]
  49. Robert J., Bismuth R., Lemaitre N., Jarlier V. ( 2006). Gentamicin-susceptible or gentamicin-resistant methicillin-resistant Staphylococcus aureus: a case-case study. Infect Control Hosp Epidemiol 27:879–883 [View Article][PubMed]
     [Google Scholar]
  50. Robinson D. A., Enright M. C. ( 2003). Evolutionary models of the emergence of methicillin-resistant Staphylococcus aureus . Antimicrob Agents Chemother 47:3926–3934 [View Article][PubMed]
     [Google Scholar]
  51. Shearer J. E., Wireman J., Hostetler J., Forberger H., Borman J., Gill J., Sanchez S., Mankin A., Lamarre J. & other authors ( 2011). Major families of multiresistant plasmids from geographically and epidemiologically diverse staphylococci. G3 (Bethesda) 1581–591 [CrossRef]
     [Google Scholar]
  52. Tennent J. M., Young H. K., Lyon B. R., Amyes S. G. B., Skurray R. A. ( 1988). Trimethoprim resistance determinants encoding a dihydrofolate reductase in clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci. J Med Microbiol 26:67–73 [View Article][PubMed]
     [Google Scholar]
  53. van Belkum A., Verkaik N. J., de Vogel C. P., Boelens H. A., Verveer J., Nouwen J. L., Verbrugh H. A., Wertheim H. F. L. ( 2009). Reclassification of Staphylococcus aureus nasal carriage types. J Infect Dis 199:1820–1826 [View Article][PubMed]
     [Google Scholar]
  54. Waldron D. E., Lindsay J. A. ( 2006). Sau1: a novel lineage-specific type I restriction-modification system that blocks horizontal gene transfer into Staphylococcus aureus and between S. aureus isolates of different lineages. J Bacteriol 188:5578–5585 [View Article][PubMed]
     [Google Scholar]
  55. Wang Y. C., Lipsitch M. ( 2006). Upgrading antibiotic use within a class: tradeoff between resistance and treatment success. Proc Natl Acad Sci U S A 103:9655–9660 [View Article][PubMed]
     [Google Scholar]
  56. Webb G. F., D’Agata E. M. C., Magal P., Ruan S. ( 2005). A model of antibiotic-resistant bacterial epidemics in hospitals. Proc Natl Acad Sci U S A 102:13343–13348 [View Article][PubMed]
     [Google Scholar]
  57. Williams L. E., Detter C., Barry K., Lapidus A., Summers A. O. ( 2006). Facile recovery of individual high-molecular-weight, low-copy-number natural plasmids for genomic sequencing. Appl Environ Microbiol 72:4899–4906 [View Article][PubMed]
     [Google Scholar]
  58. Witney A. A., Marsden G. L., Holden M. T. G., Stabler R. A., Husain S. E., Vass J. K., Butcher P. D., Hinds J., Lindsay J. A. ( 2005). Design, validation, and application of a seven-strain Staphylococcus aureus PCR product microarray for comparative genomics. Appl Environ Microbiol 71:7504–7514 [View Article][PubMed]
     [Google Scholar]
  59. Zetola N., Francis J. S., Nuermberger E. L., Bishai W. R. ( 2005). Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis 5:275–286 [View Article][PubMed]
     [Google Scholar]
  60. Zünd P., Lebek G. ( 1980). Generation time-prolonging R plasmids: correlation between increases in the generation time of Escherichia coli caused by R plasmids and their molecular size. Plasmid 3:65–69 [View Article][PubMed]
     [Google Scholar]
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Large mobile genetic elements carrying resistance genes that do not confer a fitness burden in healthcare-associated meticillin-resistant Staphylococcus aureus
Microbiology 159, 1661 (2013); https://doi.org/10.1099/mic.0.068551-0
/content/journal/micro/10.1099/mic.0.068551-0
/content/journal/micro/10.1099/mic.0.068551-0
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