Fig 2.

OC8 circular genome map (A) and genetic status of IS256 copies on the genome (B). In A, OC8 genome information includes MRSA-typing targets, phages, SaPIs, mobile genetic elements, including IS256, virulence, drug resistance, and inversion. Genes (products) described on the genome map are: spa, protein A; coa, coagulase; psmα, phenol-soluble modulin α (cytolytic peptide); rsp, AraC family transcriptional regulator; rot, repressor of toxins; ebh, extracellular matrix-binding protein (very large surface-anchored protein/giant protein); grl, DNA topoisomerase IV (quinoplone resistance); hla, α-hemolysin (Hla); map, map protein; hld, δ-hemolysin (Hld); agr, accessory gene regulator; fos, fosfomycin resistance protein; tca, teicoplanin resistance-associated membrane protein; sbi, IgG-binding protein; hlg, γ-hemolysin (Hlg); fnb, fibronectin-binding protein; ica, intercellular adhesion protein A (biofilm formation); gyr, DNA gyrase (quinoplone resistance). The staphylococcal complement inhibitor (SCIN) gene (scn), staphylokinase (SAK) gene (sak), and superantigen SEA gene (sea) were carried by phage Sa3, and the β-hemolysin (Hlb) gene (hlb) was split by a phage Sa3 insertion. The OC8 genome carried 19 copies of IS256; they are numbered (① to ⑲), as shown in the figure. IS256-enriched hot spots are marked in pink. A large genomic inversion (MbIN), relative to USA300 FPR3757 (GenBank accession number CP000255), occurred between IS256⑤ and IS256⑰; the inverted region is marked with a red thick arrow. Due to MbIN, the genomic island vSAβ, which carried three IS256 (⑥, ⑰, and ⑱), was split into two parts located far from each other. In B, the direction of the IS256 insertion is shown by arrows. Attachment (att) site sequences appear on both sides of IS256 as direct repeats (DRs) upon insertion [48,49]; the att sequences of 19 IS256 copies were all divergent from each other. The att sequences in capital letters were present as att at the corresponding position of USA300 FPR3757, which lacked IS256. Regarding unusual att sets, the red mark (box) indicates heterogeneous att sequences on the left and right sides, and the green mark indicates the imperfect DRs of att. The 26-bp imperfect terminal inverted repeats of IS256 were identical for 19 IS256 copies, except for IS256③, which had one base change.