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J Bacteriol. 1996 Sep; 178(18): 5464–5471.
PMCID: PMC178368

Role of mecA transcriptional regulation in the phenotypic expression of methicillin resistance in Staphylococcus aureus.

Abstract

The gene required for methicillin resistance in staphylococci, mecA, encodes the low-affinity penicillin-binding protein 2a (PBP2a). Transcriptional regulation of mecA is accomplished in some isolates by mecR1 and mecI, cotranscribed chromosomal genes that encode a putative signal transducer and a transcriptional repressor, respectively. Two Staphylococcus aureus strains that have identical mecR1-mecI nucleotide sequences, BMS1 and N315P, both exhibit low-level, heterotypic expression of methicillin resistance and contain no beta-lactamase coregulatory sequences. mecR1-mecI was amplified from BMS1 by PCR and was shown to be functional on a high-copy-number plasmid when introduced into an S. aureus strain with a deleted mecR1-mecI locus. Cloned mecR1-mecI repressed phenotypic expression of methicillin resistance, mecA transcription and PBP2a production and mediated PBP2a induction in response to certain beta-lactam antibiotics. However, mecR1-mecI had different regulatory activities in its native chromosomal location in N315P compared with those in BMS1. Uninduced mecA transcription was markedly repressed in N315P, and mecI inactivation increased mecA transcription and PBP2a production 5- and 40-fold, respectively. Furthermore, the N315P phenotype changed from low-level, heterotypic resistance with intact mecI to high-level, homotypic resistance in strains with disrupted mecI. In contrast, uninduced BMS1 produced abundant mecA transcript and PBP2a, while the disruption of mecI had no effect on phenotype and little effect on mecA transcription or PBP2a production. Thus, mecI-mediated repression of mecA appears to be dysfunctional in BMS1 because of the presence or absence of additional regulatory cofactors. Furthermore, heterotypic resistance expression in this strain is independent of mecA transcriptional regulation.

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Selected References

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  • Archer GL, Niemeyer DM. Origin and evolution of DNA associated with resistance to methicillin in staphylococci. Trends Microbiol. 1994 Oct;2(10):343–347. [PubMed]
  • Archer GL, Niemeyer DM, Thanassi JA, Pucci MJ. Dissemination among staphylococci of DNA sequences associated with methicillin resistance. Antimicrob Agents Chemother. 1994 Mar;38(3):447–454. [PMC free article] [PubMed]
  • Archer GL, Thanassi JA, Niemeyer DM, Pucci MJ. Characterization of IS1272, an insertion sequence-like element from Staphylococcus haemolyticus. Antimicrob Agents Chemother. 1996 Apr;40(4):924–929. [PMC free article] [PubMed]
  • Bennett PM, Chopra I. Molecular basis of beta-lactamase induction in bacteria. Antimicrob Agents Chemother. 1993 Feb;37(2):153–158. [PMC free article] [PubMed]
  • Berger-Bächi B. Expression of resistance to methicillin. Trends Microbiol. 1994 Oct;2(10):389–393. [PubMed]
  • Berger-Bächi B, Strässle A, Gustafson JE, Kayser FH. Mapping and characterization of multiple chromosomal factors involved in methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1992 Jul;36(7):1367–1373. [PMC free article] [PubMed]
  • Berger-Bächi B, Strässle A, Kayser FH. Characterization of an isogenic set of methicillin-resistant and susceptible mutants of Staphylococcus aureus. Eur J Clin Microbiol. 1986 Dec;5(6):697–701. [PubMed]
  • Bolivar F, Rodriguez RL, Greene PJ, Betlach MC, Heyneker HL, Boyer HW, Crosa JH, Falkow S. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene. 1977;2(2):95–113. [PubMed]
  • Chambers HF, Hackbarth CJ. 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. [PMC free article] [PubMed]
  • Chambers HF, Hackbarth CJ, Drake TA, Rusnak MG, Sande MA. Endocarditis due to methicillin-resistant Staphylococcus aureus in rabbits: expression of resistance to beta-lactam antibiotics in vivo and in vitro. J Infect Dis. 1984 Jun;149(6):894–903. [PubMed]
  • Chambers HF, Hartman BJ, 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. [PMC free article] [PubMed]
  • Cohen S, Sweeney HM. Constitutive penicillinase formation in Staphylococcus aureus owing to a mutation unlinked to the penicillinase plasmid. J Bacteriol. 1968 Apr;95(4):1368–1374. [PMC free article] [PubMed]
  • de Lencastre H, Tomasz A. Reassessment of the number of auxiliary genes essential for expression of high-level methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1994 Nov;38(11):2590–2598. [PMC free article] [PubMed]
  • Drlica K, Rouviere-Yaniv J. Histonelike proteins of bacteria. Microbiol Rev. 1987 Sep;51(3):301–319. [PMC free article] [PubMed]
  • Gough JA, Murray NE. Sequence diversity among related genes for recognition of specific targets in DNA molecules. J Mol Biol. 1983 May 5;166(1):1–19. [PubMed]
  • Hackbarth CJ, Chambers HF. blaI and blaR1 regulate beta-lactamase and PBP 2a production in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1993 May;37(5):1144–1149. [PMC free article] [PubMed]
  • Hackbarth CJ, Miick C, Chambers HF. Altered production of penicillin-binding protein 2a can affect phenotypic expression of methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1994 Nov;38(11):2568–2571. [PMC free article] [PubMed]
  • Hartman BJ, Tomasz A. Expression of methicillin resistance in heterogeneous strains of Staphylococcus aureus. Antimicrob Agents Chemother. 1986 Jan;29(1):85–92. [PMC free article] [PubMed]
  • Hattori M, Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. [PubMed]
  • Hiramatsu K. Molecular evolution of MRSA. Microbiol Immunol. 1995;39(8):531–543. [PubMed]
  • 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. [PubMed]
  • Horinouchi S, Weisblum B. Nucleotide sequence and functional map of pE194, a plasmid that specifies inducible resistance to macrolide, lincosamide, and streptogramin type B antibodies. J Bacteriol. 1982 May;150(2):804–814. [PMC free article] [PubMed]
  • Kasatiya SS, Baldwin JN. Nature of the determinant of tetracycline resistance in Staphylococcus aureus. Can J Microbiol. 1967 Aug;13(8):1079–1086. [PubMed]
  • Lee CY, Buranen SL, Ye ZH. Construction of single-copy integration vectors for Staphylococcus aureus. Gene. 1991 Jul 15;103(1):101–105. [PubMed]
  • Matsuhashi M, Song MD, 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. [PMC free article] [PubMed]
  • Morton TM, Eaton DM, Johnston JL, Archer GL. DNA sequence and units of transcription of the conjugative transfer gene complex (trs) of Staphylococcus aureus plasmid pGO1. J Bacteriol. 1993 Jul;175(14):4436–4447. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Novick R. Properties of a cryptic high-frequency transducing phage in Staphylococcus aureus. Virology. 1967 Sep;33(1):155–166. [PubMed]
  • Rouch DA, Byrne ME, Kong YC, Skurray RA. The aacA-aphD gentamicin and kanamycin resistance determinant of Tn4001 from Staphylococcus aureus: expression and nucleotide sequence analysis. J Gen Microbiol. 1987 Nov;133(11):3039–3052. [PubMed]
  • Ryffel C, Kayser FH, Berger-Bächi B. Correlation between regulation of mecA transcription and expression of methicillin resistance in staphylococci. Antimicrob Agents Chemother. 1992 Jan;36(1):25–31. [PMC free article] [PubMed]
  • Sharma VK, Johnston JL, Morton TM, Archer GL. Transcriptional regulation by TrsN of conjugative transfer genes on staphylococcal plasmid pGO1. J Bacteriol. 1994 Jun;176(12):3445–3454. [PMC free article] [PubMed]
  • Speer BS, Shoemaker NB, Salyers AA. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Clin Microbiol Rev. 1992 Oct;5(4):387–399. [PMC free article] [PubMed]
  • Suzuki E, Kuwahara-Arai K, Richardson JF, Hiramatsu K. Distribution of mec regulator genes in methicillin-resistant Staphylococcus clinical strains. Antimicrob Agents Chemother. 1993 Jun;37(6):1219–1226. [PMC free article] [PubMed]
  • Tesch W, Ryffel C, Strässle A, Kayser FH, 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Vazquez GJ, Archer GL. Antibiotic therapy of experimental Staphylococcus epidermidis endocarditis. Antimicrob Agents Chemother. 1980 Feb;17(2):280–285. [PMC free article] [PubMed]
  • Wittman V, Wong HC. Regulation of the penicillinase genes of Bacillus licheniformis: interaction of the pen repressor with its operators. J Bacteriol. 1988 Jul;170(7):3206–3212. [PMC free article] [PubMed]
  • Yanisch-Perron C, Vieira J, Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. [PubMed]

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