Origins and Evolution of Methicillin-Resistant Staphylococcus aureus Clonal Lineages

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Abstract
Most methicillin-resistant Staphylococcus aureus (MRSA) isolates identified among blood isolates collected in Denmark between 1957 and 1970 belonged to either phage group III or the closely related 83A complex and had a PSTM antibiotype (resistance to penicillin [P], streptomycin [S], tetracycline [T], and methicillin [M]). Recently, some of these isolates were shown to have the same genetic backgrounds as contemporary epidemic MRSA isolates, and Danish methicillin-susceptible S. aureus (MSSA) isolates from the 1960s with a PST antibiotype were proposed to have been the recipients of the mecA gene in those lineages. In this study, we investigated the genetic backgrounds of isolates from the 83A complex that were fully susceptible or resistant to penicillin only in order to try to trace the evolutionary trajectory of contemporary MRSA lineages. We also studied MSSA and MRSA isolates from other phage groups in order to investigate if they had the potential to develop into contemporary MRSA clones. Most susceptible or penicillin-resistant isolates from phage group III or the 83A complex belonged to sequence type 8 (ST8) or ST5, while four isolates were ST254. STs 30, 45 and 25 were represented by MSSA isolates from other phage groups, which also included several singletons. Representatives of most of the current major epidemic MRSA lineages were identified among fully susceptible isolates collected in the 1960s, suggesting that these were MSSA lineages which carried genetic traits important for superior epidemicity before the acquisition of methicillin resistance.

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