Origins and evolution of methicillin-resistant Staphylococcus aureus clonal lineages

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.

FIG. 1.

Distribution of S. aureus infection isolates collected between 1957 and 1973 in Denmark (n = 5,304) by the most prevalent antibiotypes and phage groups I (279 isolates), II (590 isolates), III (923 isolates), 83A complex (1,552 isolates), 80 complex (1,094 isolates), type 95 (9 isolates), 94,96 complex (39 isolates), mixed (362 isolates), and nontypeable (NT; 233 isolates).

FIG. 2.

Diagram of clonal groups defined for MSSA isolates with the eBURST algorithm. Clonal groups were defined by the less stringent approach: five or more shared alleles of the seven MLST loci. Single genotypes that do not correspond to any clonal group were identified as singletons. Each number represents an MLST ST. Blue numbers represent STs found in the present study, while black or white numbers represent STs which were already present in the database. The ST of the predicted ancestral genotype (predicted founder) is associated with a blue circle whose area indicates the prevalence of the ST in the entire MLST database. In parentheses, the number of isolates with a particular ST deposited in the database is followed by the number of isolates with that ST found in our study. Although STs 36 (EMRSA-16), 247 (Iberian clone), and 239 (Brazilian clone) have not been found among MSSA isolates in the present study, their numbers have been included in the diagram because of their epidemiological importance and relationship to STs in this work.

FIG. 3.

Model for the early evolution of MRSA in CC8. The scheme was based on the molecular typing of MRSA and MSSA isolates collected between 1957 and 1973 in Denmark. Arrows indicate the directions and changes between genotypes.