Genome sequence of a recently emerged, highly transmissible, multi-antibiotic- and antiseptic-resistant variant of methicillin-resistant Staphylococcus aureus, sequence type 239 (TW)

Abstract

The 3.1-Mb genome of an outbreak methicillin-resistant Staphylococcus aureus (MRSA) strain (TW20) contains evidence of recently acquired DNA, including two large regions (635 kb and 127 kb). The strain is resistant to a wide range of antibiotics, antiseptics, and heavy metals due to resistance genes encoded on mobile genetic elements and also mutations in housekeeping genes.

FIG. 1.

Schematic circular diagram of the S. aureus TW20 chromosome. Key for the circular diagram (outer to inner): outer colored segments on the gray outer ring represent genomic islands and horizontally acquired DNA (see the key in the figure); scale (in Mb); annotated CDSs colored according to predicted function are shown on a pair of concentric circles, representing both coding strands; S. aureus reciprocal Fasta matches shared with the S. aureus strains: MRSA252, (accession number BX571856) (16), MSSA476 (accession number BX571857) (16), MW2 (accession number BA000033) (4), N315 (accession number BA000018) (20), Mu50 (accession number BA000017) (20), Mu3 (accession number AP009324) (23), COL (accession number CP000046) (13), NCTC8325 (accession number CP000253) (14), USA3000 FPR3757 (accession number CP000255) (11), JH9 (accession number CP000703) (22), Newman (accession number AP009351) (3), and RF122 (accession number AJ938182) (15); regions of the chromosome derived from a CC8 ancestor (light green) or the CC30 ancestor (brown). Color coding for TW20 CDS functions: dark blue, pathogenicity/adaptation; black, energy metabolism; red, information transfer; dark green, surface associated; cyan, degradation of large molecules; magenta, degradation of small molecules; yellow, central/intermediary metabolism; pale green, unknown; pale blue, regulators; orange, conserved hypothetical; brown, pseudogenes; pink, phage and IS elements; gray, miscellaneous.

FIG. 2.

Comparative analysis of the TW20 plasmid pTW20_1 with the mer operon of the TW20 SCC region. Pairwise comparisons of the TW20 SCC region containing the mer operon from the TW20 chromosome (top) with the TW20 plasmid pTW20_1 (bottom) using the Artemis Comparison Tool (ACT) (9) are shown. The colored bars separating each sequence (red and blue) represent matches identified by BlastN (1); red lines link matches in the same orientation, and blue lines link matches in the reverse orientation. CDSs associated with metal and drug resistance are marked, as are IS431 elements. Colored bars at the top of the figure indicate parts of the sequence found in the SCCmercury (blue) and SCCmec (green) elements, including ΨTn554 (yellow), that make up this region.

FIG. 3.

Comparative analysis of φSPβ-like(TW20) prophage with the S. epidermidis RP62a φSPß-like prophage. Pairwise BlastN comparison of the S. aureus TW20 prophage φSPβ-like(TW20) region from the TW20 chromosome (top) with the S. epidermidis RP62a φSPß-like prophage region from the RP62a chromosome (bottom) (13) displayed in ACT is shown. The extent of the φSPβ-like(TW20) prophage in the TW20 sequence, which extends from SATW20_20290 to SATW20_21850, is marked by the pink horizontal bar.