Emergence of Staphylococcus aureus Carrying Multiple Drug Resistance Genes on a Plasmid Encoding Exfoliative Toxin B

Abstract

ABSTRACTWe report the complete nucleotide sequence and analysis of pETBTY825, aStaphylococcus aureusTY825 plasmid encoding exfoliative toxin B (ETB).S. aureusTY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4(∼30 kbp). Genomic comparison of the plasmids shows that pETBTY825has the archetype pETBTY4as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6′)/aph(2″)], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producingS. aureusstrains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses foraac(6′)/aph(2″) andmsrAusing purified plasmid preparations. The ETB-producingS. aureusstrains began to display high resistance to GM, which was parallel with the detection ofaac(6′)/aph(2″) andmecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however,msrAwas hardly detected in ETB-producingS. aureusstrains, and only five isolates were positive for bothaac(6′)/aph(2″) andmsrA. In this study, we report the emergence of a fusion plasmid carrying the toxin geneetband drug resistance genes. Prevalence of the pETBTY825carrier may further increase the clinical threat, since ETB-producingS. aureusis closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.