Pecifically in human or swine MRSA (Fig. 2). Among these genes, 96 genes were present in greater than 80 human MRSA while 6 genes were present in all swine MRSA. Host-specific genes contained 56 pathogenicity island genes (3 in vSa3, 5 in vSa4, 2 in Tn5801, 6 in vSaa, 10 in vSab, 2 in vSac, and 28 in phage wSa3), 10 phage-related genes, 4 resistant-related genes (fmhC, mecR1, mecI, and lytN) [11], 2 global regulators (sarH2 and sarH3), 5 transposes, 2 helicases, and 24 hypothetical proteins. Among these genes, several continuous genes formed 10 clusters (i.e. more than three contiguous genes) (Table 1 and Fig. 3). Seven clusters belonged to known genomic islands vSa3, vSa4, vSaa, vSab, Tn5801, and phage wSa3. Human-specific genomic island phage wSa3 contained immune evasion complex genes that encode the staphylokinase (sak). This prophage, integrated into bhemolysin locus, has been found in most isolates infecting humans but not animals [12]. Human-specific genomic island vSab included six virulence genes, namely, splA, splB, splC, splD, splF, and lukD, which enhanced the virulence of MRSA and facilitated human infection. In addition, type I restriction modification (R-M)Comparative Genomics of Predominant MRSA Clones in ChinaFrom 1994 to 2000 in Beijing, the most predominant MRSA clone was ST239-spa t037. Since 2000, ST239-spa t030 has rapidly replaced t037 and has become the major clone [10]. A comparison of 11 spa t037 and 5 spa t030 genome information showed that 309 variable genes were variable in 16 strains. Ninety-eight genes are more frequent in spa t030, and 2 genes (SAV0059 and SAV0864) are more frequent in spa t037. Fifty-four pathogenic island genes (10 in vSa4, 8 in vSa3, 4 in vSaa, and 30 in phage wSa3), 12 phage-related genes, and 1 transcription-related gene were included in these genes. For ST239-spa t030 specific genes, four gene clusters (Table 1) may contribute to the MRSA evolution from ST239-spa t037 to ST239-spa t030 (Fig. 3). These geneComparative Genomics of Staphylococcus aureusFigure 1. Cluster analysis of 50 strains via microarray. (A) Phylogenetic tree analysis of 50 strains. White bars: gene absence, black bars: gene presence, red bars: no information. (B) Characteristics of 50 strains. Cluster analysis indicated that all of the 50 strains were clustered into seven different complexes. doi:10.1371/journal.pone.0053341.gclusters belonged to previously characterized genomic islands vSa4, phage wSa1, and wSa3. Duvelisib site Notably, phage wSa3 was unique to ST239- spa t030 MRSA and carried two toxin genes, sak (staphylokinase) and sep (enterotoxin P), which may contribute to its increased virulence and epidemiology [13]. Besides, most variable genes found in these islands have unknown functions. Except for ST239, ST5 was the E7449 web second predominant clone in China. We analyzed the presence of antibiotic-resistant clusters via large-scale PCR validation in 43 ST239 or ST5 MRSA strains and 5 ST59 MRSA strains. Greater than 60 of the predominantclones ST239 and ST5 existed these antibiotic-resistant clusters, but none of ST59 strains existed these clusters. The carriage of multiple antibiotic resistance gene clusters probably enhanced the adaptability and competitiveness of ST239 and ST5, as well as contributed to the prevalence in China.DiscussionExtensive genetic variations were identified among 50 strains representing the major dominant lineages of S. aureus from humanComparative Genomics of Staphylococcus aureusFigure 2. Genes.Pecifically in human or swine MRSA (Fig. 2). Among these genes, 96 genes were present in greater than 80 human MRSA while 6 genes were present in all swine MRSA. Host-specific genes contained 56 pathogenicity island genes (3 in vSa3, 5 in vSa4, 2 in Tn5801, 6 in vSaa, 10 in vSab, 2 in vSac, and 28 in phage wSa3), 10 phage-related genes, 4 resistant-related genes (fmhC, mecR1, mecI, and lytN) [11], 2 global regulators (sarH2 and sarH3), 5 transposes, 2 helicases, and 24 hypothetical proteins. Among these genes, several continuous genes formed 10 clusters (i.e. more than three contiguous genes) (Table 1 and Fig. 3). Seven clusters belonged to known genomic islands vSa3, vSa4, vSaa, vSab, Tn5801, and phage wSa3. Human-specific genomic island phage wSa3 contained immune evasion complex genes that encode the staphylokinase (sak). This prophage, integrated into bhemolysin locus, has been found in most isolates infecting humans but not animals [12]. Human-specific genomic island vSab included six virulence genes, namely, splA, splB, splC, splD, splF, and lukD, which enhanced the virulence of MRSA and facilitated human infection. In addition, type I restriction modification (R-M)Comparative Genomics of Predominant MRSA Clones in ChinaFrom 1994 to 2000 in Beijing, the most predominant MRSA clone was ST239-spa t037. Since 2000, ST239-spa t030 has rapidly replaced t037 and has become the major clone [10]. A comparison of 11 spa t037 and 5 spa t030 genome information showed that 309 variable genes were variable in 16 strains. Ninety-eight genes are more frequent in spa t030, and 2 genes (SAV0059 and SAV0864) are more frequent in spa t037. Fifty-four pathogenic island genes (10 in vSa4, 8 in vSa3, 4 in vSaa, and 30 in phage wSa3), 12 phage-related genes, and 1 transcription-related gene were included in these genes. For ST239-spa t030 specific genes, four gene clusters (Table 1) may contribute to the MRSA evolution from ST239-spa t037 to ST239-spa t030 (Fig. 3). These geneComparative Genomics of Staphylococcus aureusFigure 1. Cluster analysis of 50 strains via microarray. (A) Phylogenetic tree analysis of 50 strains. White bars: gene absence, black bars: gene presence, red bars: no information. (B) Characteristics of 50 strains. Cluster analysis indicated that all of the 50 strains were clustered into seven different complexes. doi:10.1371/journal.pone.0053341.gclusters belonged to previously characterized genomic islands vSa4, phage wSa1, and wSa3. Notably, phage wSa3 was unique to ST239- spa t030 MRSA and carried two toxin genes, sak (staphylokinase) and sep (enterotoxin P), which may contribute to its increased virulence and epidemiology [13]. Besides, most variable genes found in these islands have unknown functions. Except for ST239, ST5 was the second predominant clone in China. We analyzed the presence of antibiotic-resistant clusters via large-scale PCR validation in 43 ST239 or ST5 MRSA strains and 5 ST59 MRSA strains. Greater than 60 of the predominantclones ST239 and ST5 existed these antibiotic-resistant clusters, but none of ST59 strains existed these clusters. The carriage of multiple antibiotic resistance gene clusters probably enhanced the adaptability and competitiveness of ST239 and ST5, as well as contributed to the prevalence in China.DiscussionExtensive genetic variations were identified among 50 strains representing the major dominant lineages of S. aureus from humanComparative Genomics of Staphylococcus aureusFigure 2. Genes.
