Genomic comparison between Staphylococcus aureus GN strains clinically isolated from a familial infection case: 1S1272 transposition through a novel inverted repeat-replacing mechanism

A bacterial insertion sequence (IS) is a mobile DNA sequence carrying only the transposase gene (tnp) that acts as a mutator to disrupt genes, alter gene expressions, and cause genomic rearrangements. Canonical ISs have historically been characterized by their terminal inverted repeats (IRs), which may form a stem-loop structure, and duplications of a short (non-IR) target sequence at both ends, called target site duplications (TSDs). The IS distributions and virulence potentials of Staphylococcus aureus genomes in familial infection cases are unclear. Here, we determined the complete circular genome sequences of familial strains from a Panton-Valentine leukocidin (PVL)-positive ST50/agr4 S. aureus (GN) infection of a 4-year old boy with skin abscesses. The genomes of the patient strain (GN1) and parent strain (GN3) were rich for canonical IS 1272 with terminal IRs, both having 13 commonly -existing copies (ce-IS 1272). Moreover, GN1 had a newly-inserted IS 1272 (niIS 1272) on the PVL-converting prophage, while GN3 had two copies of ni-IS 1272 within the DNA helicase gene and near rot. The GN3 genome also had a small deletion. The targets of ni-IS 1272 transposition were IR structures, in contrast with previous canonical ISs. There were no TSDs. Based on a database search, the targets for ce-IS 1272 were IRs or nonIRs. IS 1272 included a larger structure with tandem duplications of the left (IRL) side sequence; tnp included minor cases of a long fusion form and truncated form. One ce-IS 1272 was associated with the segments responsible for immune evasion and drug resistance. Regarding virulence, GN1 expressed cytolytic peptides (phenol-soluble modulin a and delta-hemolysin) and PVL more strongly than some other familial strains. These results suggest that IS1272transposes through an IR-replacing mechanism, with an irreversible process unlike that of canonical transpositions, resulting in genomic variations, and that, among the familial strains, the patient strain has strong virulence potential based on community -associated virulence factors.