Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Dec;40(12):2680–2685. doi: 10.1128/aac.40.12.2680

Suppression of methicillin resistance in a mecA-containing pre-methicillin-resistant Staphylococcus aureus strain is caused by the mecI-mediated repression of PBP 2' production.

K Kuwahara-Arai 1, N Kondo 1, S Hori 1, E Tateda-Suzuki 1, K Hiramatsu 1
PMCID: PMC163603  PMID: 9124822

Abstract

The mechanism of methicillin susceptibility was studied in Staphylococcus aureus N315P, a pre-methicillin-resistant S. aureus strain that is susceptible to methicillin, despite the presence of mecA in the chromosome. In the presence of mec regulator genes mecI and mecR1, transcription of the mecA gene was not inducible by the addition of methicillin to the culture medium. Inactivation of the mecI gene function by replacing it with tetL made N315P express heterogeneous-type methicillin resistance. The subclone, in which the mecI gene was replaced, subclone P delta I, produced 12 times greater amounts of mecA gene transcripts and 8.5 times more PBP 2' protein than N315P. These data indicate that the mecI gene-encoded repression of mecA gene transcription is responsible for the apparent methicillin susceptibility phenotype of pre-methicillin-resistant S. aureus N315P.

Full Text

The Full Text of this article is available as a PDF (401.5 KB).

Selected References

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

  1. 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]
  2. 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]
  3. Chang S., Cohen S. N. High frequency transformation of Bacillus subtilis protoplasts by plasmid DNA. Mol Gen Genet. 1979 Jan 5;168(1):111–115. doi: 10.1007/BF00267940. [DOI] [PubMed] [Google Scholar]
  4. Dyer D. W., Iandolo J. J. Rapid isolation of DNA from Staphylococcus aureus. Appl Environ Microbiol. 1983 Jul;46(1):283–285. doi: 10.1128/aem.46.1.283-285.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hackbarth C. J., Kocagoz T., Kocagoz S., Chambers H. F. Point mutations in Staphylococcus aureus PBP 2 gene affect penicillin-binding kinetics and are associated with resistance. Antimicrob Agents Chemother. 1995 Jan;39(1):103–106. doi: 10.1128/aac.39.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Hiramatsu K., Asada K., Suzuki E., Okonogi K., Yokota T. Molecular cloning and nucleotide sequence determination of the regulator region of mecA gene in methicillin-resistant Staphylococcus aureus (MRSA). FEBS Lett. 1992 Feb 24;298(2-3):133–136. doi: 10.1016/0014-5793(92)80039-j. [DOI] [PubMed] [Google Scholar]
  8. Hiramatsu K., Kihara H., Yokota T. Analysis of borderline-resistant strains of methicillin-resistant Staphylococcus aureus using polymerase chain reaction. Microbiol Immunol. 1992;36(5):445–453. doi: 10.1111/j.1348-0421.1992.tb02043.x. [DOI] [PubMed] [Google Scholar]
  9. Hiramatsu K. Molecular evolution of MRSA. Microbiol Immunol. 1995;39(8):531–543. doi: 10.1111/j.1348-0421.1995.tb02239.x. [DOI] [PubMed] [Google Scholar]
  10. Hürlimann-Dalel R. L., Ryffel C., Kayser F. H., Berger-Bächi B. Survey of the methicillin resistance-associated genes mecA, mecR1-mecI, and femA-femB in clinical isolates of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1992 Dec;36(12):2617–2621. doi: 10.1128/aac.36.12.2617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. McDougal L. K., Thornsberry C. The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins. J Clin Microbiol. 1986 May;23(5):832–839. doi: 10.1128/jcm.23.5.832-839.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Murakami K., Tomasz A. Involvement of multiple genetic determinants in high-level methicillin resistance in Staphylococcus aureus. J Bacteriol. 1989 Feb;171(2):874–879. doi: 10.1128/jb.171.2.874-879.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Saito M., Sekiguchi K., Yajima R., Hina M., Doss R. C., Kanno H. Immunological detection of penicillin-binding protein 2' of methicillin-resistant staphylococci by using monoclonal antibodies prepared from synthetic peptides. J Clin Microbiol. 1995 Sep;33(9):2498–2500. doi: 10.1128/jcm.33.9.2498-2500.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sekiguchi K., Saito M., Yajima R. Detection of methicillin-resistant Staphylococcus aureus (MRSA) with antibodies against synthetic peptides derived from penicillin-binding protein 2'. Microbiol Immunol. 1995;39(8):545–550. doi: 10.1111/j.1348-0421.1995.tb02240.x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Suzuki E., Hiramatsu K., Yokota T. Survey of methicillin-resistant clinical strains of coagulase-negative staphylococci for mecA gene distribution. Antimicrob Agents Chemother. 1992 Feb;36(2):429–434. doi: 10.1128/aac.36.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Suzuki E., Kuwahara-Arai K., Richardson J. F., Hiramatsu K. Distribution of mec regulator genes in methicillin-resistant Staphylococcus clinical strains. Antimicrob Agents Chemother. 1993 Jun;37(6):1219–1226. doi: 10.1128/aac.37.6.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Tomasz A., Drugeon H. B., de Lencastre H. M., Jabes D., McDougall L., Bille J. New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity. Antimicrob Agents Chemother. 1989 Nov;33(11):1869–1874. doi: 10.1128/aac.33.11.1869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tomasz A., Nachman S., Leaf H. Stable classes of phenotypic expression in methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother. 1991 Jan;35(1):124–129. doi: 10.1128/aac.35.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ubukata K., Yamashita N., Konno M. Occurrence of a beta-lactam-inducible penicillin-binding protein in methicillin-resistant staphylococci. Antimicrob Agents Chemother. 1985 May;27(5):851–857. doi: 10.1128/aac.27.5.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. de Jonge B. L., Tomasz A. Abnormal peptidoglycan produced in a methicillin-resistant strain of Staphylococcus aureus grown in the presence of methicillin: functional role for penicillin-binding protein 2A in cell wall synthesis. Antimicrob Agents Chemother. 1993 Feb;37(2):342–346. doi: 10.1128/aac.37.2.342. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES