title: Modification of homogeneous resistance in a methicillin-resistant strain of Staphylococcus aureus by acquisition of a beta-lactamase encoding plasmid.
abstract: Nearly all clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) are heterogeneously resistant and produce beta-lactamases which generally are plasmid mediated. In order to study the role of beta-lactamase plasmids in the expression of methicillin resistance, a beta-lactamase plasmid from Enterococcus faecalis HH22 (pBEM10) was transferred into a homogeneously resistant, beta-lactamase-negative strain of MRSA (MUSC284). By single disc diffusion testing at 42 degrees C, beta-lactamase producing transconjugants (SA-MM1) were found to be more susceptible than the parent strain to methicillin, imipenem, SCH 34343 and cloxacillin, but more resistant to piperacillin. The heterogeneity observed in transconjugants was not affected by the addition of clavulanic acid, indicating that beta-lactamase itself was not responsible for this effect. By population analysis over 50% of MUSC284 colonies and less than 1% of SA-MM1 colonies remained viable after incubation at 42 degrees C in agar plates containing 25 mg/l of cloxacillin. Cured derivatives of SA-MM1 reverted to homogeneous resistance to beta-lactam antibiotics as observed in the initial parenteral strain MUSC284. Thus, the introduction of a beta-lactamase coding plasmid into a homogeneously resistant MRSA yielded transconjugants which resembled heterogeneously resistant strains of MRSA. These results suggest that regulatory genes, capable of altering the expression of methicillin resistance, may be located on beta-lactamase plasmids commonly found in these organisms.
authors.affiliation: Memorial Hospital, Brown University Program in Medicine, Providence, Rhode Island.
authors.forename: S M
authors.initials: SM
authors.lastname: Opal
authors.forename: J M
authors.initials: JM
authors.lastname: Boyce
authors.forename: A A
authors.initials: AA
authors.lastname: Medeiros
authors.forename: K H
authors.initials: KH
authors.lastname: Mayer
authors.forename: L W
authors.initials: LW
authors.lastname: Lyhte
mesh_terms: D002876:Chromosomes, Bacterial; D003023:Cloxacillin / Q000494:pharmacology; D003227:Conjugation, Genetic; D003470:Culture Media; D013293:Enterococcus faecalis / Q000187:drug effects; D008712:Methicillin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010957:Plasmids; D012293:Rifampin / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D003470:Culture Media; D001618:beta-Lactamases; D003023:Cloxacillin; D008712:Methicillin; D012293:Rifampin