The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA) is explored in this study, which uses multilocus sequence typing (MLST) and the BURST algorithm to analyze 912 MRSA and methicillin-susceptible S. aureus (MSSA) isolates from 20 countries. The study identifies 11 major MRSA clones within five groups of related genotypes. Using BURST, the researchers infer the putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor. The study also examines the methicillin resistance gene (mecA) and its acquisition, revealing that major MRSA clones have arisen repeatedly from successful epidemic MSSA strains. Isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes. Methicillin was introduced in 1959 to treat infections caused by penicillin-resistant S. aureus. In 1961, reports of methicillin-resistant S. aureus (MRSA) were made in the UK, and MRSA isolates were soon recovered from other European countries, and later from Japan, Australia, and the United States. MRSA is now a problem in hospitals worldwide and is increasingly recovered from nursing homes and the community. The methicillin resistance gene (mecA) encodes a methicillin-resistant penicillin-binding protein that is not present in susceptible strains and is believed to have been acquired from a distantly related species. mecA is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec), of which four forms have been described that differ in size and genetic composition. The study shows that the origins of the major MRSA clones are still poorly understood. Kreiswirth et al. proposed that all MRSAs were descended from a single ancestral S. aureus strain that acquired mecA, but more recent studies show that some MRSAs are very divergent, implying that mecA has been transferred between S. aureus lineages. The data from MLST can be used to probe the evolutionary and population biology of bacterial pathogens and to predict ancestral genotypes and patterns of evolutionary descent within groups of related genotypes. The study applied MLST to an international collection of 359 MRSA isolates and compared these to a collection of 553 methicillin-susceptible S. aureus (MSSAs). The study demonstrates the limited number of major EMRSA genotypes and provides an unambiguous method for characterizing MRSA and GISA clones and a rational nomenclature. The study also identifies the ancestral MRSA clone and itsThe evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA) is explored in this study, which uses multilocus sequence typing (MLST) and the BURST algorithm to analyze 912 MRSA and methicillin-susceptible S. aureus (MSSA) isolates from 20 countries. The study identifies 11 major MRSA clones within five groups of related genotypes. Using BURST, the researchers infer the putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor. The study also examines the methicillin resistance gene (mecA) and its acquisition, revealing that major MRSA clones have arisen repeatedly from successful epidemic MSSA strains. Isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes. Methicillin was introduced in 1959 to treat infections caused by penicillin-resistant S. aureus. In 1961, reports of methicillin-resistant S. aureus (MRSA) were made in the UK, and MRSA isolates were soon recovered from other European countries, and later from Japan, Australia, and the United States. MRSA is now a problem in hospitals worldwide and is increasingly recovered from nursing homes and the community. The methicillin resistance gene (mecA) encodes a methicillin-resistant penicillin-binding protein that is not present in susceptible strains and is believed to have been acquired from a distantly related species. mecA is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec), of which four forms have been described that differ in size and genetic composition. The study shows that the origins of the major MRSA clones are still poorly understood. Kreiswirth et al. proposed that all MRSAs were descended from a single ancestral S. aureus strain that acquired mecA, but more recent studies show that some MRSAs are very divergent, implying that mecA has been transferred between S. aureus lineages. The data from MLST can be used to probe the evolutionary and population biology of bacterial pathogens and to predict ancestral genotypes and patterns of evolutionary descent within groups of related genotypes. The study applied MLST to an international collection of 359 MRSA isolates and compared these to a collection of 553 methicillin-susceptible S. aureus (MSSAs). The study demonstrates the limited number of major EMRSA genotypes and provides an unambiguous method for characterizing MRSA and GISA clones and a rational nomenclature. The study also identifies the ancestral MRSA clone and its