The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones

Abstract

The key genetic component of methicillin resistance, the mecA determinant, is not native to Staphylococcus aureus. Thus, the evolution of methicillin-resistant S. aureus (MRSA) must have begun with the acquisition of the mecA determinant from an unknown heterologous source some time before the first reported appearance of MRSA isolates in clinical specimens in the U.K. and Denmark (in the early 1960s). We compared the genetic backgrounds and phenotypes of a group of methicillin-susceptible S. aureus (MSSA) isolates to the properties of MRSA strains isolated in Denmark and the U.K. during the same time period, and also to the genetic profiles of contemporary epidemic clones of MRSA. All early MRSA isolates resembled a large group of the early MSSA blood isolates in phenotypic and genetic properties, including phage group, antibiotype (resistance to penicillin, streptomycin, and tetracycline), pulsed-field gel electrophoresis pattern, and spaA type and multilocus sequence type, strongly suggesting that the early MSSA examined here represented the progeny of a strain that served as one of the first S. aureus recipients of the methicillin-resistance determinant in Europe. The genetic background of this group of early MSSA isolates was also very similar to that of the widely disseminated contemporary "Iberian clone" of MRSA, suggesting that genetic determinants present in early MSSA and essential for some aspects of the epidemicity and/or virulence of these strains may have been retained by this highly successful contemporary MRSA lineage.

Figure 1

Sequential appearance of M-susceptible and M-resistant blood isolates of S. aureus belonging to phage group III and the related 83A complex (in Denmark). ■, P-S-T-M isolates; ♦, P-S-T isolates. The numbers plotted represent all S. aureus blood isolates identified in Denmark during the particular period.

Figure 2

(A) Comparison of PFGE patterns from historically early MSSA and MRSA isolates from Denmark and the U.K. and representatives of the Iberian, Pediatric, and New York clones of MRSA. Lanes 2–12 show early MSSA strains (Table 1). Lanes 13 and 15–22 show early MRSA strains (Table 2). Lanes 23–25 show contemporary MRSA (Table 3). Strains used in A are underlined in Tables 1, 2, and 3. Lane 2, E213; lane 3, E228; lane 4, E306; lane 5, E803; lane 6, E1215; lane 7, E1907; lane 8, E2104; lane 9, E1410; lane 10, E3008; lane 11, E2260; lane 12, E2251; lane 13, E2672; lane 15, E2125; lane 16, E2213; lane 17, E3015; lane 18, E3150; lane 19, E3520; lane 20, E4278; lane 21, ST61/6219; lane 22, ST63/458; lane 23, Iberian clone HPV107 (19); lane 24, Pediatric clone HDE288 (23); lane 25, New York clone BK2464 (24). Lanes 1, 14, and 26 show strain NCTC8325 used as molecular weight standard. (B) Computer-generated dendrogram of the PFGE patterns shown in A. Results are from analysis of similarity by Jacquard's coefficient; clustering was done by the minimum linkage method.