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. 1992 Jan;36(1):25–31. doi: 10.1128/aac.36.1.25

Correlation between regulation of mecA transcription and expression of methicillin resistance in staphylococci.

C Ryffel 1, F H Kayser 1, B Berger-Bächi 1
PMCID: PMC189220  PMID: 1375449

Abstract

Total RNA was used to study the effect of penicillinase plasmid pI524 and of mecR, the regulatory region located on the methicillin resistance determinant (mec), on the expression of mecA, the gene coding for the low-affinity penicillin-binding protein PBP2', in methicillin-resistant staphylococci. In the present report, we show that the regulation of methicillin resistance occurs primarily at the level of mecA transcription and that in the presence of intact plasmid pI524 or mecR, the gene undergoes negative control. The relative amount of mecA mRNA present during exponential growth in uninduced cultures matches the type of mecA regulation and decreases in the following order: constitutive greater than pI524 greater than mecR-dependent mecA expression. Induction of mecA by methicillin is faster in pI524- than in mecR-controlled strains. The overall mRNA half-life is similar for all strains analyzed. Our results indicate that methicillin resistance under mecR control in certain staphylococcal strains could escape detection by the standard disk diffusion test and broth microdilution test because of the very slow derepression of the mecA gene. This finding is of importance for the clinical detection of this type of methicillin resistance.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Archer G. L., Pennell E. Detection of methicillin resistance in staphylococci by using a DNA probe. Antimicrob Agents Chemother. 1990 Sep;34(9):1720–1724. doi: 10.1128/aac.34.9.1720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barberis-Maino L., Berger-Bächi B., Weber H., Beck W. D., Kayser F. H. IS431, a staphylococcal insertion sequence-like element related to IS26 from Proteus vulgaris. Gene. 1987;59(1):107–113. doi: 10.1016/0378-1119(87)90271-x. [DOI] [PubMed] [Google Scholar]
  3. Barberis-Maino L., Ryffel C., Kayser F. H., Berger-Bächi B. Complete nucleotide sequence of IS431mec in Staphylococcus aureus. Nucleic Acids Res. 1990 Sep 25;18(18):5548–5548. doi: 10.1093/nar/18.18.5548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beck W. D., Berger-Bächi B., Kayser F. H. Additional DNA in methicillin-resistant Staphylococcus aureus and molecular cloning of mec-specific DNA. J Bacteriol. 1986 Feb;165(2):373–378. doi: 10.1128/jb.165.2.373-378.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Belasco J. G., Higgins C. F. Mechanisms of mRNA decay in bacteria: a perspective. Gene. 1988 Dec 10;72(1-2):15–23. doi: 10.1016/0378-1119(88)90123-0. [DOI] [PubMed] [Google Scholar]
  6. Berger-Bächi B. Genetics of methicillin resistance in Staphylococcus aureus. J Antimicrob Chemother. 1989 May;23(5):671–673. doi: 10.1093/jac/23.5.671. [DOI] [PubMed] [Google Scholar]
  7. Berger-Bächi B., Strässle A., Kayser F. H. Characterization of an isogenic set of methicillin-resistant and susceptible mutants of Staphylococcus aureus. Eur J Clin Microbiol. 1986 Dec;5(6):697–701. doi: 10.1007/BF02013308. [DOI] [PubMed] [Google Scholar]
  8. Boyce J. M., Medeiros A. A., Papa E. F., O'Gara C. J. Induction of beta-lactamase and methicillin resistance in unusual strains of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1990 Jan;25(1):73–81. doi: 10.1093/jac/25.1.73. [DOI] [PubMed] [Google Scholar]
  9. Chambers H. F., Hackbarth C. J. Effect of NaCl and nafcillin on penicillin-binding protein 2a and heterogeneous expression of methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1987 Dec;31(12):1982–1988. doi: 10.1128/aac.31.12.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chambers H. F., Hartman B. J., Tomasz A. Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin. J Clin Invest. 1985 Jul;76(1):325–331. doi: 10.1172/JCI111965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cookson B., Phillips I. Methicillin-resistant staphylococci. Soc Appl Bacteriol Symp Ser. 1990;19:55S–70S. doi: 10.1111/j.1365-2672.1990.tb01798.x. [DOI] [PubMed] [Google Scholar]
  13. Gaisford W. C., Reynolds P. E. Methicillin resistance in Staphylococcus epidermidis. Relationship between the additional penicillin-binding protein and an attachment transpeptidase. Eur J Biochem. 1989 Oct 20;185(1):211–218. doi: 10.1111/j.1432-1033.1989.tb15104.x. [DOI] [PubMed] [Google Scholar]
  14. Gilman M. Z., Chamberlin M. J. Developmental and genetic regulation of Bacillus subtilis genes transcribed by sigma 28-RNA polymerase. Cell. 1983 Nov;35(1):285–293. doi: 10.1016/0092-8674(83)90231-3. [DOI] [PubMed] [Google Scholar]
  15. Hartman B. J., Tomasz A. Low-affinity penicillin-binding protein associated with beta-lactam resistance in Staphylococcus aureus. J Bacteriol. 1984 May;158(2):513–516. doi: 10.1128/jb.158.2.513-516.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Madiraju M. V., Brunner D. P., Wilkinson B. J. Effects of temperature, NaCl, and methicillin on penicillin-binding proteins, growth, peptidoglycan synthesis, and autolysis in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1987 Nov;31(11):1727–1733. doi: 10.1128/aac.31.11.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Matsuhashi M., Song M. D., Ishino F., Wachi M., Doi M., Inoue M., Ubukata K., Yamashita N., Konno M. Molecular cloning of the gene of a penicillin-binding protein supposed to cause high resistance to beta-lactam antibiotics in Staphylococcus aureus. J Bacteriol. 1986 Sep;167(3):975–980. doi: 10.1128/jb.167.3.975-980.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matthews P. R., Reed K. C., Stewart P. R. The cloning of chromosomal DNA associated with methicillin and other resistances in Staphylococcus aureus. J Gen Microbiol. 1987 Jul;133(7):1919–1929. doi: 10.1099/00221287-133-7-1919. [DOI] [PubMed] [Google Scholar]
  19. Murakami K., Nomura K., Doi M., Yoshida T. Production of low-affinity penicillin-binding protein by low- and high-resistance groups of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1987 Sep;31(9):1307–1311. doi: 10.1128/aac.31.9.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Murphy E., Novick R. P. Physical mapping of Staphylococcus aureus penicillinase plasmid pI524: characterization of an invertible region. Mol Gen Genet. 1979 Aug;175(1):19–30. doi: 10.1007/BF00267851. [DOI] [PubMed] [Google Scholar]
  21. Okonogi K., Noji Y., Kondo M., Imada A., Yokota T. Emergence of methicillin-resistant clones from cephamycin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Nov;24(5):637–645. doi: 10.1093/jac/24.5.637. [DOI] [PubMed] [Google Scholar]
  22. Patel A. H., Foster T. J., Pattee P. A. Physical and genetic mapping of the protein A gene in the chromosome of Staphylococcus aureus 8325-4. J Gen Microbiol. 1989 Jul;135(7):1799–1807. doi: 10.1099/00221287-135-7-1799. [DOI] [PubMed] [Google Scholar]
  23. Rossi L., Tonin E., Cheng Y. R., Fontana R. Regulation of penicillin-binding protein activity: description of a methicillin-inducible penicillin-binding protein in Staphylococcus aureus. Antimicrob Agents Chemother. 1985 May;27(5):828–831. doi: 10.1128/aac.27.5.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rowland S. J., Dyke K. G. Tn552, a novel transposable element from Staphylococcus aureus. Mol Microbiol. 1990 Jun;4(6):961–975. doi: 10.1111/j.1365-2958.1990.tb00669.x. [DOI] [PubMed] [Google Scholar]
  25. Ryffel C., Bucher R., Kayser F. H., Berger-Bächi B. The Staphylococcus aureus mec determinant comprises an unusual cluster of direct repeats and codes for a gene product similar to the Escherichia coli sn-glycerophosphoryl diester phosphodiesterase. J Bacteriol. 1991 Dec;173(23):7416–7422. doi: 10.1128/jb.173.23.7416-7422.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ryffel C., Tesch W., Birch-Machin I., Reynolds P. E., Barberis-Maino L., Kayser F. H., Berger-Bächi B. Sequence comparison of mecA genes isolated from methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Gene. 1990 Sep 28;94(1):137–138. doi: 10.1016/0378-1119(90)90481-6. [DOI] [PubMed] [Google Scholar]
  27. Song M. D., Wachi M., Doi M., Ishino F., Matsuhashi M. Evolution of an inducible penicillin-target protein in methicillin-resistant Staphylococcus aureus by gene fusion. FEBS Lett. 1987 Aug 31;221(1):167–171. doi: 10.1016/0014-5793(87)80373-3. [DOI] [PubMed] [Google Scholar]
  28. Staeheli P., Danielson P., Haller O., Sutcliffe J. G. Transcriptional activation of the mouse Mx gene by type I interferon. Mol Cell Biol. 1986 Dec;6(12):4770–4774. doi: 10.1128/mcb.6.12.4770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tesch W., Ryffel C., Strässle A., Kayser F. H., Berger-Bächi B. Evidence of a novel staphylococcal mec-encoded element (mecR) controlling expression of penicillin-binding protein 2'. Antimicrob Agents Chemother. 1990 Sep;34(9):1703–1706. doi: 10.1128/aac.34.9.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tesch W., Strässle A., Berger-Bächi B., O'Hara D., Reynolds P., Kayser F. H. Cloning and expression of methicillin resistance from Staphylococcus epidermidis in Staphylococcus carnosus. Antimicrob Agents Chemother. 1988 Oct;32(10):1494–1499. doi: 10.1128/aac.32.10.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ubukata K., Nonoguchi R., Matsuhashi M., Konno M. Expression and inducibility in Staphylococcus aureus of the mecA gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein. J Bacteriol. 1989 May;171(5):2882–2885. doi: 10.1128/jb.171.5.2882-2885.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ubukata K., Nonoguchi R., Song M. D., Matsuhashi M., Konno M. Homology of mecA gene in methicillin-resistant Staphylococcus haemolyticus and Staphylococcus simulans to that of Staphylococcus aureus. Antimicrob Agents Chemother. 1990 Jan;34(1):170–172. doi: 10.1128/aac.34.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Utsui Y., Yokota T. Role of an altered penicillin-binding protein in methicillin- and cephem-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1985 Sep;28(3):397–403. doi: 10.1128/aac.28.3.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Utsui Y., Yokota T. Role of an altered penicillin-binding protein in methicillin- and cephem-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1985 Sep;28(3):397–403. doi: 10.1128/aac.28.3.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. de Lencastre H., Sá Figueiredo A. M., Urban C., Rahal J., Tomasz A. Multiple mechanisms of methicillin resistance and improved methods for detection in clinical isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Apr;35(4):632–639. doi: 10.1128/aac.35.4.632. [DOI] [PMC free article] [PubMed] [Google Scholar]

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