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Journal of Bacteriology, December 2001, p. 6862-6868, Vol. 183, No. 23
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.23.6862-6868.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Transcription of the Gene Mediating Methicillin Resistance in Staphylococcus aureus (mecA) Is Corepressed but Not Coinduced by Cognate mecA and beta -Lactamase Regulators

Tanya K. McKinney,1,2,dagger Vijay K. Sharma,1,2,Dagger William A. Craig,1 and Gordon L. Archer1,2,*

Departments of Medicine1 and Microbiology/Immunology,2 Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia 23298-0049

Received 21 May 2001/Accepted 11 September 2001

Resistance to beta -lactam antibiotics in staphylococci is mediated by mecA and blaZ, genes encoding a penicillin-binding protein (PBP2a) with low beta -lactam affinity and beta -lactamase, respectively. The mec and bla regulators, mecR1-mecI and blaR1-blaI, respectively, encode inducer-repressors with sufficient amino acid homology to suggest that they could coregulate PBP2a production. In order to test this hypothesis, plasmids containing mec and bla regulatory sequences were introduced into Staphylococcus aureus containing a chromosomal mecA-lacZ transcriptional fusion. Corepression was confirmed by demonstrating a gene dosage-dependent reduction in beta -galactosidase activity by either MecI or BlaI and additive repression when both were present. Both MecI-MecI and BlaI-BlaI homodimer and MecI-BlaI heterodimer interactions were demonstrated in the yeast two-hybrid assay, and purified MecI and BlaI protected the same mec promoter-operator sequences. However, MecI was approximately threefold more effective at mecA-lacZ transcriptional repression than was BlaI. While MecI and BlaI displayed similar activity as repressors of mecA transcription, there was a marked difference between MecR1 and BlaR1 in the rate and specificity of induction. Induction through BlaR1 by a beta -lactam was 10-fold greater than through MecR1 at 60 min and was 81% of maximal by 2 h, while induction through MecR1 never exceeded 20% of maximal. Furthermore, complementation studies showed that MecI- or BlaI-mediated mecA transcriptional repression could be relieved by induction through homologous but not heterologous sensor-inducer proteins, demonstrating the repressor specificity of induction.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, Virginia Commonwealth University, Medical College of Virginia, Box 980049, Room 7-082, Sanger Hall, 1101 E. Marshall St., Richmond, VA 23298-0049. Phone: (804) 828-9711. Fax: (804) 828-3097. E-mail: garcher{at}hsc.vcu.edu.

dagger Present address: Xavier University of Louisiana, Department of Biology, New Orleans, LA 70125.

Dagger Present address: United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, IA 50010.

Journal of Bacteriology, December 2001, p. 6862-6868, Vol. 183, No. 23
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.23.6862-6868.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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