Susceptibility to six metal ions—cadmium (Cd), mercury (Hg), arsenate (Asa), arsenite (Asi), antimony (Sb) and zinc (Zn)—was tested in 23 independent isolates of methicillin-resistant (MRSA) obtained from Guy's Hospital (GH) during 1984–1986, which included 10 isolates of the UK epidemic EMRSA-1 strain. Strains were also tested for resistance to antibiotics and the nucleic-acid-binding compounds propamidine isethionate and ethidium bromide. A further 19 methicillin-resistant isolates, including 10 EMRSA-1 were obtained from other sources. Ten methicillin-sensitive, antibiotic sensitive isolates were from Guy's Hospital. Resistance to Hg was associated with methicillin resistance in 19 of the 20 EMRSA-1 isolates, all of which were resistant to Cd. Resistance to Cd and Hg was found in 13 out of 22 other MRSA isolates. Hg resistance was not present in the methicillin-sensitive isolates which were often (13 out of 19) moderately resistant to Cd. Multiple resistance to metal ions, including resistance to Hg, Asa, Asi and Sb, was uncommon. Resistance to Cd (MIC>32mg/L or 8–16mg/L) was associated with increased resistance to Zn. In 11 of the consecutive MRSA isolates from Guy's Hospital seven distinct strains were recognised by phage type. Methicillin resistance in these strains varied from 16 to 1024 mg/L at 30°C with a 2–8 fold lower minimum inhibitory concentration at 37°C indicating some degree of heterogeneity. Representatives of the EMRSA-1 strain had the higher levels of resistance. Loss of methicillin resistance occurred in 0.2–5.0% of colonies tested after storage at room temperature in 10 of these isolates. In some EMRSA-1 strains this loss was associated with loss of Cd, Zn and, usually, Hg resistance, and a 4-fold reduction in resistance to tetracycline. These resistance determinants were not transferred by transduction of plasmids from these strains and plasmid-free strains retained these markers, indicating that a chromosomal region is involved. These findings support evidence for a close relationship between the EMRSA-1 strain in the UK and the recent epidemic MRSA strain in eastern Australia. In the strains which lost methicillin resistance independently of other markers, Cd resistance and β-lactamase production were plasmid encoded, as shown by co-elimination and co-transduction of these markers. In addition to Cd and penicillin resistance, the markers encoded by these plasmids included resistance to Asa, Asi and Sb in two strains, resistance to Hg, propamidine isethionate and ethidium bromide in a further two isolates, and for resistance to Hg, Asa, Asi and Sb, kanamycin, neomycin and streptomycin, and erythromycin and clindamycin in one strain. Methicillin resistance was transduced from strain GH34 to strain 80CR5 with phage 80. MICs of methicillin (1024 mg/L) were higher for transductants than the donor strain (32–64 mg/L) at 30°C and showed little heterogeneity when tested at 37°C.


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