Genetic analysis of high-level mupirocin resistance in the ST80 clone of community-associated meticillin-resistant Staphylococcus aureus

Abstract

Four community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) isolates expressing high-level mupirocin resistance (MIC .1024 mg l "1 ) were isolated from four sites of a diabetic patient and characterized for the genetic location of their resistance determinants and typed using PFGE, staphylococcal cassette chromosome mec (SCCmec), the coagulase gene and multilocus sequence typing to ascertain their relatedness. The presence of genes for resistance to high-level mupirocin (mupA), tetracycline (tetK) and fusidic acid (far1), PantonValentine leukocidin (PVL), accessory gene regulators (agr) and capsular polysaccharide (cap) were detected in PCR assays. The isolates were resistant to kanamycin, streptomycin, tetracycline, fusidic acid and cadmium acetate, and harboured mupA, tetK, far1, PVL, agr3 and cap8. They had identical PFGE patterns and coagulase gene type, possessed the type IV SCCmec element and belonged to sequence type 80 (ST80). However, they had three different plasmid profiles: (i) 28.0 and 26.0 kb; (ii) 28.0, 21.0 and 4.0 kb; and (iii) 41.0 and 4.0 kb. Genetic studies located the resistance to tetracycline, fusidic acid and cadmium acetate on the 28 kb plasmid and mupA on the related non-conjugative 26 and 21 kb plasmids. One of the 21 kb mupirocin-resistance plasmids was derived from the~41 kb plasmid during transfer experiments. The emergence of high-level mupirocin resistance in the ST80-SCCmec IV MRSA clone demonstrates the increasing capacity of CA-MRSA clones to acquire resistance to multiple antibacterial agents. The presence of different plasmid profiles in genetically identical isolates creates difficulty in the interpretation of typing results and highlights the weakness of using plasmid analysis as the sole method for strain typing.

Synergism between a Novel Chimeric Lysin and Oxacillin Protects against Infection by Methicillin-Resistant Staphylococcus aureus

“…A greater-than 2-log drop was seen 1 h after a single treatment compared to the level of buffer alone. The currently accepted S. aureus decolonization regimen includes treatment with mupirocin ointment nasally for 5 days, but recolonization and inadequate clearance often result because of increasing resistance to the antibiotic or poor patient compliance (6,42). The fact that ClyS works as a potent decolonizing agent suggests that lysin therapy is a viable treatment option in specific highrisk populations, such as in hospitals and in nursing homes, etc., and may aid in decreasing primary and secondary infection rates.…”

Characterisation of MRSA strains isolated from patients in a hospital in Riyadh, Kingdom of Saudi Arabia

“…PVL-positive CC80-IV has been dubbed the European CA-MRSA strain as it is widespread although sporadically detected across several European countries. However, it appears to be more predominant in the Middle East and Maghreb (North African) countries being detected not only in Saudi Arabia but also in Abu Dhabi [2], Kuwait [37], Lebanon [9], Tunisia [11] and Algeria [12]. …”

Community-acquired methicillin-resistant Staphylococcus aureus: community transmission, pathogenesis, and drug resistance

“…Fusidic acid resistance, mediated by fusA, fusB, or fusC genes, is one of the genetic and phenotypic characteristics [9,133,134]. Currently, high-level mupirocinresistant strains, whose MIC levels were [1,024 lg/ml, emerged in Kuwait, suggesting the difficulty of eradication of ST80 CA-MRSA [135]. This was mediated by different sizes (21 and 26 kb) of plasmids with mupA (high-level mupirocin resistance gene).…”