Abstract
Abbreviations: CA, community-associated; CC, clonal complex; HVR, hypervariable region; J, junkyard; MRSA, meticillin-resistant Staphylococcus aureus; MSSA, meticillin-sensitive Staphylococcus aureus; SCCmec, staphylococcal cassette chromosome mec; ST, sequence type.
The GenBank/EMBL/DDBJ accession numbers for the complete SCCmec sequence of the ST72 clone and the mec element sequence of the ST1 clone are EU437549 and EU437550, respectively.
The key to the appearance of meticillin-resistant S. aureus (MRSA) is the acquisition of mecA encoding PBP2A, which has been shown to be part of a mobile element referred to as staphylococcal cassette chromosome mec (SCCmec) (Hartman & Tomasz, 1984; Ito et al., 1999, 2003). The main types of SCCmec are defined by the combination of the mec complex with the ccr locus (Ito et al., 2001, 2004; Okuma et al., 2002; Oliveira et al., 2006a; Takano et al., 2008). New types and subtypes have been reported, with diverse recombination of the mec complex, the ccr types and the junkyard (J) regions (Chongtrakool et al., 2006; Heusser et al., 2007; Hisata et al., 2005; Ito et al., 2003; Shore et al., 2005).
Community-associated (CA)-MRSA strains have emerged as a major concern with regard to MRSA infections (Etienne, 2005; Gillet et al., 2002; Ho et al., 2004; Tristan et al., 2007; Vandenesch et al., 2003). However, in South Korea, there is limited information on the emergence of CA-MRSA strains. A recently reported study on MRSA in South Korea during 2004–2005 showed that there were two prevalent CA-MRSA clones [clonal complex (CC) 1 and sequence type (ST) 72] that carried type IVA SCCmec (Park et al., 2007). The multiplex type IVA was first reported by Oliveira & de Lencastre (2002). In the multiplex pattern (downstream common sequence, pUB110 locus and mecA are amplified), type IVA appears to be related to IA, II and IV. Shore et al. (2005) reported multiplex type IVA carrying class A mec complex variants. However, type IVA found in South Korea was reported to harbour class B mec complex or variants (Park et al., 2007). Chongtrakool et al. (2006) proposed a new nomenclature for SCCmec type in which type IVA was described as 2B.N.2; however, the genetic variations in the class B mec element, the ccr type and the J regions were not fully examined, and the authors stated that the data for the mec class and ccr type had been given tentatively.
Type IVA SCCmec has not been classified clearly into types and subtypes to date. Here, we have described the genetic characteristics of type IVA found in South Korea and investigated its genetic relationship with other types. We have also reported two variants of type IVA.
Bacterial strains. For analysis of the two subtypes of SCCmec IVA, we used strains cm11 ST72 and cm14 (ST1); these STs have frequently been detected in CA-MRSA strains in South Korea (Park et al., 2007). For the comparative study of the distribution of aminoglycoside-resistance genes and virulence-associated genes, we used 23 isolates of CC1 (ST1, ST493 and ST573) and 22 isolates of the ST72 clone, as reported previously (Park et al., 2007).Sequencing of the mecA complex of SCCmec from CA-MRSA clones. A single PCR method, as described elsewhere (Hisata et al., 2005; Okuma et al., 2002), was performed for comparison of type IVA from strains cm11 and cm14. The class B mec complexes of strains cm11 and cm14 were amplified and sequenced with primers as follows: IS5 (5'-AACGCCACTCATAACATATGGAA-3') and mA6 (5'-TATACCAAACCCGACAAC-3') for the IS1272-mecA region, mAnew1 (5'-TGGAATTAACGTGGAGACGA-3') and mAnew2 (5'-AACGTTGTAACCACCCCAAG-3') for mecA, and mA1 (5'-TGCTATCCACCCTCAAACAGG-3') and IS2 (5'-TGAGGTTATTCAGATATTTCGATGT-3') for the mecA-IS431mec region (Hiramatsu et al., 1992; Katayama et al., 2001; Okuma et al., 2002; Park et al., 2007).
Long-range PCR and primer-walking sequencing. For analysis of the whole sequence of SCCmec from strain cm11, we adopted a long-range PCR-based sequencing method by expanding the long PCR system using an Expand cloning kit (Roche). The primers used were as follows: ILF (5'-TCGTCTTCATCAACTTCA-3'), ccrAR (5'-CTCTTAAGGCGTTGACAA-3'), ccrAF (5'-GGATCAAGCTTTCGACCGACTCAAG-3') and IS1272R (5'-TCCTCGGACAGACATCCGAGTG-3') designed based on the sequence with GenBank accession number AB245470 in the upstream region; IS5, mAnew2, mAnew1 and IS2 in the mecA complex (Katayama et al., 2001; Okuma et al., 2002; Park et al., 2007); and pub1F (5'-AGCTGAATAAGAACGGTGCTC-3'), pubR (5'-ACATACCAACACTTCAACGCACC-3'), pub2F (5'-CCTTAAGGAACGTACAGACGGCT-3') and orfxR (5'-TCCACATCAAATGATGCGGGTTG-3') designed based on the sequences with GenBank accession numbers D86934 and AP009324 in the downstream region. Gap filling and sequencing of the left and right extremities of SCCmec by DNA walking was carried out with a SpeedUp premix kit (Seegene). Primers 15666F (5'-TGAAATCTGATGAAGAAAAGTTGG-3') and 15666R (5'-CAGGACTTGAACTGGCAGAA-3'), designed based on the sequence with GenBank accession number EU272085 [strain 15666 of meticillin-sensitive S. aureus (MSSA) ST72], were used for analysis of the insertion site of SCCmec.
Sequence analysis. Sequence data were assembled, and homology searches were performed using BLASTN and BLASTP (). The ORFs were predicted and translated using ORF Finder (). GenBank accession numbers AB037671, AB033763, AB063172, AB063173, AB097677, AB127982, AB266531, AB266532, AF411935, AJ810120, AJ810121, AM292304, CP000029, D86934, DQ106887 and EU437549 for ccrA were used for phylogenetic analysis of the ccrA nucleotide sequence (1350 nt). Multiple sequence alignments were performed with ClustalW2 () (Larkin et al., 2007). Phylogenetic and molecular evolutionary analyses were conducted with MEGA version 3.1 (Kumar et al., 2004) using the neighbour-joining method. The Jukes–Cantor parameter and the γ parameter 1.0 were used for the nucleotide substitution model.
Profiling of virulence-associated genes, aminoglycoside resistance-associated genes and antimicrobial susceptibilities. Enterotoxin and surface protein encoding genes, and aminoglycoside-resistance-associated genes from 55 isolates of CC1 and ST72 were evaluated as described by Choi et al. (2003), Jarraud et al. (2002) and Vancraeynest et al. (2004). Variation in the enterotoxin gene island (egc) was determined as described by Thomas et al. (2006). Antimicrobial susceptibilities were determined using the disc diffusion method, as recommended by the Clinical and Laboratory Standards Institute (CLSI, 2006).
Nucleotide sequence accession numbers. Nucleotide sequences determined in the present study were deposited in GenBank (http://www.ncbi.nlm.nih.gov/Genbank/) under accession numbers EU437549 (the complete SCCmec sequence of the ST72 clone) and EU437550 (the mec element sequence of the ST1 clone).
Molecular characteristics and antibiotic susceptibility of ST72 and CC1 isolatesRecently, Kim et al. (2007) and Park et al. (2007) reported that multiplex type IVA was found in ∼43 and ∼53 % of CA-MRSA isolates in South Korea, respectively. In their studies, type IVA was the most prevalent type in CA-MRSA and was found mainly in clinical isolates belonging to ST72 and CC1 (Kim et al., 2007; Park et al., 2007). Their characteristics including virulence and antibiotic-resistance patterns are summarized in Table 1. Some of the SCCmec PCR typing and antibiotic susceptibility results were included in the findings of a previous study (Park et al., 2007). The profile of the enterotoxins showed that CC1 isolates carried seh (>95 %) and ST72 carried an egc variant harbouring seu2. There were different antibiotics-susceptibility patterns in ST72 and CC1 strains, especially for gentamicin (Table 1); this was probably due to the presence of aac(6')/aph(2') in CC1 isolates (Table 1). Although both clones (ST72 and CC1) carried ant(4') at the pUB110 locus of SCCmec IVA (Table 1), ANT(4')-Ia encoded by ant(4') is not related to gentamicin resistance but is associated with resistance to amikacin, tobramycin, dibekacin, isepamicin and kanamycin (Vakulenko & Mobashery, 2003). However, AAC(6')-Ie–APH(2')-Ia encoded by aac(6')/aph(2') confers resistance to virtually all aminoglycosides including gentamicin, but not for streptomycin (Vakulenko & Mobashery, 2003).
Table 1. Molecular characteristics and antibiotic-resistance patterns of major SCCmec IVA clones
Genetic variation of SCCmec type IVA
There were some variations in the PCR results for class B mec and ccrAB identified in ST72 and CC1 strains (Table 1). We compared the class B mec complex and ccrAB variations in cm11 (ST72) and cm14 (ST1) strains. The overlapping single SCCmec PCR products were sequenced to compare the differences in more detail (Fig. 1). Variations were found in the class B mec complex of strain cm11: a transposase 20 family gene (tnp20, ORF C017; Table 2) was inserted, and the hypervariable region (HVR) and ugpQ were deleted, when compared with other class B mec elements (Fig. 1). tnp20 was almost identical (∼99.6 %) to SCCpbp4, commonly reported in Staphylococcus epidermidis strains; it has also recently been reported in a Swedish MRSA strain (JCSC6668; Berglund et al., 2009). The class B.3 mec, of strain JCSC6668, was similar to that of strain cm11, except for deletion of the HVR and ugpQ (Fig. 1). The deletion of the HVR was similar to the class B mec element of type IA (Fig. 1).
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Table 2. List of ORFs of SCCmec type IVA from the ST72 clone
In contrast, strain cm14 (ST1) carried a typical class B mec (IS1272–ΔmecR1–mecA–HVR–IS431), when compared with other SCCmec IV types (Fig. 1). It had the mecA upstream region, similar to SCCmec type IVc, but had linearized plasmid pUB110 in the downstream region, which was different from that of IVc (Table 1).
ccr allotyping has been useful for examination of the phylogenetic relationships among SCCmec types (Oliveira et al., 2006b, 2008). Therefore, we investigated the genetic variation and relationship of ccrAB of type IVA. The nucleotide sequence of the ccrAB locus in strain cm14 was almost identical (>99 %) to that of the type IVc variant. The ccrB2 sequence from strain cm11 was identical (100 %) to that of IVc (MR108); however, ccrA2 was slightly different, with a 96 % identity determined by BLASTP. Comparison of type IVA and other ccrA allotypes showed that most of the type IV subtypes clustered in one closely related group distinct from those of type II, with the exception of type IVb (Fig. 2). The ccrA2 of type IVA (cm11) clustered with type IV subtypes and was much closer to that of SCCmec IVg (Fig. 2). In the nucleotide sequence analysis of ccrA2, type IVA should be phylogenetically closer to type IV than to type II.
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SCCmec type IVA of strain cm11 (ST72) could provide evidence of exchange and recombination of SCC DNA in staphylococci inter- and intra-species
We examined the whole SCCmec structure of strain cm11 (ST72), which appeared to be similar to SCCmec type 2B.N.2 (Fig. 3a). Twenty-one ORFs in SCCmec were identified by ORF Finder and BLASTP; most had >98 % identity with previously identified staphylococcal genes, except for ccrA2 (Table 2). The dispersed ORFs of the left extremity region were almost identical to those of type IVc (MR108) and SCCpbp4 (S. epidermidis ATCC 12228) (Fig. 3b, Table 2). The J3 region with linearized pUB110 was almost identical to that of type IA and II (Table 2). The organization of the class B variant and the J3 region in this structure may be more similar to that of type IA than other types, but the ccr type and other J regions seemed to be derived from type IV (Fig. 3a). Analysis of type IVA showed a unique structure composed of the recombination of a variant class B mec element and the type 2 ccrAB with the J regions derived from type IA or II (J3) and IVc or SCCpbp4 (J1 and J2) (Fig. 3a). It has been suggested that exchange and recombination of SCC DNA probably occurs in staphylococci inter- and intra-species (Hanssen & Sollid, 2007; Hanssen et al., 2004). The genetic structure of SCCmec type IVA, from strain cm11, could provide evidence supporting both inter- and intra-species recombination.
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Analysis of the left boundary of SCCmec IVA indicates SCCmec acquisition by non-CcrAB-mediated insertion
The integration sequence and the inverted repeats at the right and left boundaries of SCCmec were identical to SCCmec type IVc (S. aureus MR108). However, the outermost sequence of the SCCmec attachment site (SCCmec attB) of the left boundary was very different from that of IVc (MR108) (Fig. 3c). The results of primer-walking studies showed that the 15 bp core sequence (SCCmec attB) and the SCCmec acquisition site of strain 15666 (MSSA ST72) were conserved surrounding the sequences at the left-end extremity of SCCmec IVA (cm11) (Fig. 3a, c). Noto et al. (2008) suggested that there could be two mechanisms for the acquisition of SCCmec; CcrAB-mediated and non-CcrAB-mediated insertion mechanisms (other integrase mechanisms or homologous recombination). For CcrAB-mediated acquisition, a specific sequence should be necessary at the surrounding boundary of the left-end extremity. However, at the left-end extremity of type IVA, there was no CcrAB-mediated specific sequence (Fig. 3c). In addition, there were no lost or gained sequences at the SCCmec acquisition site, compared with strain 15666 (Fig. 3c). These findings suggest that MSSA ST72 strains could acquire SCCmec type IVA by non-CcrAB-mediated insertion.
Epidemiological features of SCCmec type IVA strains prevalent in South Korea
The genetic diversity of CA-MRSA strains is probably due to the successful conversion of diverse MSSA lineages to MRSA by the transfer of SCCmec in the community. In particular, SCCmec type IV, the smallest structural and most diverse type, predominates among the diverse CA-MRSA strains worldwide (Robinson & Enright, 2003; Vandenesch et al., 2003). However, instead of type IV, SCCmec IVA types are the most prevalent CA-MRSA strains found in South Korea, compared with other countries (Cha et al., 2005; Kim et al., 2007; Park et al., 2007, 2008). The emergence of SCCmec type IVA strains is a major concern in the public health setting and for infection control in hospitals, and these strains have recently been shown to be spreading (Kim et al., 2007; Park et al., 2007, 2009).
Epidemiological studies of S. aureus and antibiotic use in South Korea have reported that ST72 (major SCCmec IVA clonal lineage) MSSA and MRSA strains were not frequently isolated until 2005 in South Korea (Kim et al., 2008). This suggests that IVA strains have emerged recently in South Korea. In addition, it has been reported that the antimicrobial use density of aminoglycosides was one of the highest in a survey of antimicrobial use during 2004–2007, which corresponded with the results of the Health Insurance Review and Assessment Service () in South Korea (Yoon et al., 2008). The finding that ant(4') was carried on the genetic island of type IVA by both SCCmec IVA strains (ST72 and CC1) and that aac(6')/aph(2') was carried by CC1 strains (Table 1) suggests that exposure to aminoglycosides might provide a favourable environment for the spread of SCCmec IVA strains rather than IV strains.
In conclusion, we have described two variants of SCCmec IVA, each of which showed genetic differences in the class B mec complex. In particular, the genetic organization of type IVA in ST72 strains appeared to be more related structurally to types IA (class B mec complex variation and J2 region) and IV (ccr type, J1 and J2 region) than the other types. The genetic relationship of ORFs on SCCmec type IVA suggests that the development of type IVA appears to result from the dynamic genetic exchange and recombination of SCC DNA inter- and intra-species. In the future, it will be necessary to investigate the genetic evolutionary relationships of other SCC DNAs, as well as their epidemiology, to determine how these types disseminate in community and hospital settings.
This research was supported by a grant (08152KFDA161) from the Korea Food and Drug Administration in 2008.References
Cha, H. Y., Moon, D. C., Choi, C. H., Oh, J. Y., Jeong, Y. S., Lee, Y. C., Seol, S. Y., Cho, D. T., Chang, H. H. & other authors (2005). Prevalence of the ST239 clone of methicillin-resistant Staphylococcus aureus and differences in antimicrobial susceptibilities of ST239 and ST5 clones identified in a Korean hospital. J Clin Microbiol 43, 3610–3614.
Choi, S. M., Kim, S. H., Kim, H. J., Lee, D. G., Choi, J. H., Yoo, J. H., Kang, J. H., Shin, W. S. & Kang, M. W. (2003). Multiplex PCR for the detection of genes encoding aminoglycoside modifying enzymes and methicillin resistance among Staphylococcus species. J Korean Med Sci 18, 631–636.[Medline]
Chongtrakool, P., Ito, T., Ma, X. X., Kondo, Y., Trakulsomboon, S., Tiensasitorn, C., Jamklang, M., Chavalit, T., Song, J. H. & Hiramatsu, K. (2006). Staphylococcal cassette chromosome mec (SCCmec) typing of methicillin-resistant Staphylococcus aureus strains isolated in 11 Asian countries: a proposal for a new nomenclature for SCCmec elements. Antimicrob Agents Chemother 50, 1001–1012.
CLSI (2006). Performance Standards for Antimicrobial Susceptibility Testing, sixteenth informational supplement, approved standard M100–S16. Wayne, PA: Clinical and Laboratory Standards Institute.
Dinges, M. M., Orwin, P. M. & Schlievert, P. M. (2000). Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13, 16–34.
Etienne, J. (2005). Panton–Valentine leukocidin: a marker of severity for Staphylococcus aureus infection? Clin Infect Dis 41, 591–593.[CrossRef][Medline]
Gillet, Y., Issartel, B., Vnahems, P., Foumet, J., Lina, G., Bes, M., Vandenesch, F., Piemont, Y., Brousse, N. & other authors (2002). Association between Staphylococcus aureus strains carrying gene for Panton–Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359, 753–759.[CrossRef][Medline]
Hanssen, A. M. & Sollid, J. U. (2007). Multiple staphylococcal cassette chromosomes and allelic variants of cassette chromosome recombinases in Staphylococcus aureus and coagulase-negative staphylococci from Norway. Antimicrob Agents Chemother 51, 1671–1677.
Hanssen, A. M., Kjeldsen, G. & Sollid, J. U. (2004). Local variants of staphylococcal cassette chromosome mec in sporadic methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci: evidence of horizontal gene transfer? Antimicrob Agents Chemother 48, 285–296.
Hartman, B. J. & Tomasz, A. (1984). Low-affinity penicillin-binding protein associated with β-lactam resistance in Staphylococcus aureus. J Bacteriol 158, 513–516.
Heusser, R., Ender, M., Berger-Bächi, B. & McCallum, N. (2007). Mosaic staphylococcal cassette chromosome mec containing two recombinase loci and a new mec complex, B2. Antimicrob Agents Chemother 51, 390–393.
Hiramatsu, K., Kihara, H. & Yokota, T. (1992). Analysis of borderline resistant strains of methicillin-resistant Staphylococcus aureus using polymerase chain reaction. Microbiol Immunol 36, 445–453.[Medline]
Hisata, K., Kuwahara-Arai, K., Yamanoto, M., Ito, T., Nakatomi, Y., Cui, L., Baba, T., Terasawa, M., Sotozono, C. & other authors (2005). Dissemination of methicillin-resistant staphylococci among healthy Japanese children. J Clin Microbiol 43, 3364–3372.
Ho, P. L., Tse, C. W., Mak, G. C., Chow, K. H. & Ng, T. K. (2004). Community-acquired methicillin-resistant Staphylococcus aureus arrives in Hong Kong. J Antimicrob Chemother 54, 845–846.
Ito, T., Katayama, Y. & Hiramatsu, K. (1999). Cloning and nucleotide sequence determination of the entire mec DNA of pre-methicillin-resistant Staphylococcus aureus N315. Antimicrob Agents Chemother 43, 1449–1458.
Ito, T., Katayama, Y., Asada, K., Mori, N., Tsutsumimoto, K., Tiensasitorn, C. & Hiramatsu, K. (2001). Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 45, 1323–1336.
Ito, T., Okuma, K., Ma, X. X., Yuzawa, H. & Hiramatsu, K. (2003). Insights on antibiotic resistance of Staphylococcus aureus from its whole genome: genomic island SCC. Drug Resist Updat 6, 41–52.[CrossRef][Medline]
Ito, T., Ma, X. X., Takeuchi, F., Okuma, K., Yuzawa, H. & Hiramatsu, K. (2004). Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase ccrC. Antimicrob Agents Chemother 48, 2637–2651.
Jarraud, S., Mougel, C., Thioulouse, J., Lina, G., Meugnier, H., Forey, F., Nesme, X., Etienne, J. & Vandenesch, F. (2002). Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 70, 631–641.
Katayama, Y., Ito, T. & Hiramatsu, K. (2001). Genetic organization of the chromosome region surrounding mecA in clinical staphylococcal strains: role of IS431-mediated mecI deletion in expression of resistance in mecA-carrying, low-level methicillin-resistant Staphylococcus haemolyticus. Antimicrob Agents Chemother 45, 1955–1963.
Kim, E. S., Song, J. S., Lee, H. J., Choe, P. G., Park, K. H., Cho, J. H., Park, W. B., Kim, S. H., Bang, J. H. & other authors (2007). A survey of community-associated methicillin-resistant Staphylococcus aureus in Korea. J Antimicrob Chemother 60, 1108–1114.
Kim, E. S., Kim, H. B., Lee, H. J., Jung, K. T., Lee, Y. S., Shin, D. H., Jung, S. I., Park, K. U., Park, W. B. & other authors (2008). Changing molecular epidemiology of Staphylococcus aureus in Korea over a ten-year period. In 18th European Congress of Clinical Microbiology and Infectious Diseases, Barcelona, Spain, abstract 1437.
Kumar, S., Tamura, K. & Nei, M. (2004). MEGA3: integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5, 150–163.
Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P. A., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A. & other authors (2007). ClustalW2 and CLUSTAL_X version 2. Bioinformatics 23, 2947–2948.
Lina, G., Gillet, Y., Vandenesch, F., Jones, M. E., Floret, D. & Etienne, J. (1997). Toxin involvement in staphylococcal scalded skin syndrome. Clin Infect Dis 25, 1369–1373.[Medline]
Noto, M. J., Kreiswirth, B. N., Monk, A. B. & Archer, G. L. (2008). Gene acquisition at the insertion site for SCCmec, the genomic island conferring methicillin resistance in Staphylococcus aureus. J Bacteriol 190, 1276–1283.
Novick, R. P. (2000). Pathogenicity factors and their regulation. In Gram-positive Pathogens, pp. 392–407. Edited by V. A. Fischetti, R. P. Novick, J. J. Ferretti, D. A. Portnoy & J. I. Rood. Washington, DC: American Society for Microbiology.
Okuma, K., Iwakawa, K., Turnidge, J. D., Grubb, W. B., Bell, J. M., O'Brien, F. G., Coombs, G. W., Pearman, J. W., Tenover, F. C. & other authors (2002). Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol 40, 4289–4294.
Oliveira, D. C. & de Lencastre, H. (2002). Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 46, 2155–2161.
Oliveira, D. C., Milheiriço, C. & de Lencastre, H. (2006a). Redefining a structural variant of staphylococcal cassette chromosome mec, SCCmec type VI. Antimicrob Agents Chemother 50, 3457–3459.
Oliveira, D. C., Milheiriço, C., Vinga, S. & de Lencastre, H. (2006b). Assessment of allelic variation in the ccrAB locus in methicillin-resistant Staphylococcus aureus clones. J Antimicrob Chemother 58, 23–30.
Oliveira, D. C., Santos, M., Milheiriço, C., Carriço, J. A., Vinga, S., Oliveira, A. L. & de Lencastre, H. (2008). ccrB typing tool: an online resource for staphylococci ccrB sequence typing. J Antimicrob Chemother 61, 959–964.
Papakyriacou, H., Vaz, D., Simor, A., Louie, M. & McGavin, M. J. (2000). Molecular analysis of the accessory gene regulator (agr) locus and balance of virulence factor expression in epidemic methicillin-resistant Staphylococcus aureus. J Infect Dis 181, 990–1000.[CrossRef][Medline]
Park, C., Lee, D. G., Kim, S. W., Choi, S. M., Park, S. H., Chun, H. S., Choi, J. H., Yoo, J. H., Shin, W. S. & other authors (2007). Predominance of community-associated methicillin-resistant Staphylococcus aureus strains carrying staphylococcal chromosome cassette mec type IVA in Korea. J Clin Microbiol 45, 4021–4026.
Park, C., Lee, D. G., Choi, S. M., Choi, J. H., Park, S. H., Yoo, J. H. & Shin, W. S. (2008). Comments on: a survey of community-associated methicillin-resistant Staphylococcus aureus in Korea. J Antimicrob Chemother 62, 211–212.
Park, S. H., Park, C., Yoo, J. H., Choi, S. M., Choi, J. H., Shin, H. H., Lee, D. G., Lee, S., Kim, J. & other authors (2009). Emergence of community-associated methicillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated bloodstream infections in Korea. Infect Control Hosp Epidemiol 30, 146–155.[CrossRef][Medline]
Robinson, D. A. & Enright, M. C. (2003). Evolutionary models of the emergence of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 47, 3926–3934.
Shore, A., Rossney, A. S., Keane, C. T., Enright, M. C. & Coleman, D. C. (2005). Seven novel variants of the staphylococcal chromosomal cassette mec in methicillin-resistant Staphylococcus aureus isolates from Ireland. Antimicrob Agents Chemother 49, 2070–2083.
Takano, T., Higuchi, W., Otsuka, T., Baranovich, T., Enany, S., Saito, K., Isobe, H., Dohmae, S., Ozaki, K. & other authors (2008). Novel characteristics of community-acquired methicillin-resistant Staphylococcus aureus strains belonging to multilocus sequence type 59 in Taiwan. Antimicrob Agents Chemother 52, 837–845.
Thomas, D. Y., Jarraud, S., Lemercier, B., Cozon, G., Echasserieau, K., Etienne, J., Gougeon, M. L., Lina, G. & Vandenesch, F. (2006). Staphylococcal enterotoxin-like toxins U2 and V, two new staphylococcal superantigens arising from recombination within the enterotoxin gene cluster. Infect Immun 74, 4724–4734.
Tristan, A., Bes, M., Meugnier, H., Lina, G., Bozdogan, B., Courvalin, P., Reverdy, M., Enright, M., Vandenesch, F. & Etienne, J. (2007). Global distribution of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus, 2006. Emerg Infect Dis 13, 594–600.[Medline]
Vakulenko, S. B. & Mobashery, S. (2003). Versatility of aminoglycosides and prospects for their future. Clin Microbiol Rev 16, 430–450.
Vancraeynest, D., Hermans, K. & Haesebrouck, F. (2004). Genotypic and phenotypic screening of high and low virulence Staphylococcus aureus isolates from rabbits for biofilm formation and MSCRAMMs. Vet Microbiol 103, 241–247.[CrossRef][Medline]
Vandenesch, F., Naimi, T., Enright, M. C., Lina, G., Nimmo, G. R., Heffernan, H., Liassine, N., Bes, M., Greenland, T. & other authors (2003). Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton–Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 9, 978–984.[Medline]
Yoon, Y. K., Kim, M. J., Sohn, J. W., Park, D. W., Kim, J. Y. & Chun, B. C. (2008). Surveillance of antimicrobial use and antimicrobial resistance. Infect Chemother 40, 93–101.[CrossRef]
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