Heterogeneous location of the mupA high-level mupirocin resistance gene in Staphylococcus aureus.

Epidemiologically unrelated clinical isolates of Staphylococcus aureus with high-level resistance to mupirocin (MIC > or = 512 mg/L) were studied to determine the location of the mupA resistance gene. The gene was carried on plasmids of variable size, some of which were transferable in vitro. DNA hybridisation of genomic DNA from 85 isolates showed that mupA was located on EcoRI fragments of seven different sizes; the most frequently observed fragments were 7 kb (46 isolates) or 4.1 kb (21 isolates). All isolates retained a 1.6-kb Nco I fragment that hybridised with mupA probes, but showed heterogeneous hybridisation patterns after digestion with Hinc II. These data suggested that mupA may be conserved, but that variation occurs in the flanking DNA proximal to it. Amplification of spacer regions between mupA and closest proximal copy of IS257 yielded products of variable size and was consistent with the presence of IS257 in either orientation. It is proposed that IS257-mediated events are responsible for the heterogeneity observed. The location of mupA varied between epidemiologically unrelated isolates of the same strain, including isolates of EMRSA-16 -- one of the two predominant methicillin-resistant strains in UK hospitals at the present time -- and this correlated with variations in the digestion patterns of the mupirocin resistance plasmids. The variable location of mupA should be evaluated further as a potential epidemiological tool with which to monitor the spread of high-level mupirocin resistance in EMRSA-16 or other strains of S. aureus.