Regulation of the phenotypic expression of methicillin resistance in staphylococci.

摘要

taphylococci resistant to methicillin and multiple additional antibiotics have rapidly become a major infectious threat in the hospital as well as the community. Vancomycin is the only chemotherapeutic choice for many multiresistant isolates. A clearer understanding of the regulation of methicillin resistance expression may help better explain the multiresistant phenotype. This research has examined the effect the staphylococcal regulatory regions blaR1-blaI and mecR1-mecI have on the phenotypic expression of methicillin resistance as well as on mecA transcription. Both blaR1 and mecR1 encode a signal transducer and blaI and mecI a transcriptional repressor of mecA, the gene that encodes the low-affinity penicillin binding protein, PBP2a. The mec regulatory region was cloned from BMS1, a low-level (heterotypic) methicillin resistant Staphylococcus aureus strain. When provided in multicopy, the mec regulatory region could down-regulate phenotypic expression, but when mecR1-I was inserted into the chromosome of a heterotypic strain with no such regulatory region, no change in phenotype occurred. When functional, chromosomally-encoded mecI was interrupted in two different methicillin resistant strains, there were different effects. In one strain, there was no change in phenotype while the other became markedly more resistant to methicillin. Strains with an intact mecR1-I region, either in the chromosome or on a plasmid could be induced by certain