Genomic comparison between Staphylococcus aureus GN strains clinically isolated from a familial infection case: IS1272 transposition through a novel inverted repeat-replacing mechanism

PLoS One. 2017 Nov 8;12(11):e0187288. doi: 10.1371/journal.pone.0187288. eCollection 2017.

Abstract

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" IS1272 with terminal IRs, both having 13 commonly-existing copies (ce-IS1272). Moreover, GN1 had a newly-inserted IS1272 (ni-IS1272) on the PVL-converting prophage, while GN3 had two copies of ni-IS1272 within the DNA helicase gene and near rot. The GN3 genome also had a small deletion. The targets of ni-IS1272 transposition were IR structures, in contrast with previous "canonical" ISs. There were no TSDs. Based on a database search, the targets for ce-IS1272 were IRs or "non-IRs". IS1272 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-IS1272 was associated with the segments responsible for immune evasion and drug resistance. Regarding virulence, GN1 expressed cytolytic peptides (phenol-soluble modulin α and δ-hemolysin) and PVL more strongly than some other familial strains. These results suggest that IS1272 transposes 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.

Publication types

  • Comparative Study

MeSH terms

  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics
  • Base Sequence
  • Child, Preschool
  • Chromosome Mapping
  • Cluster Analysis
  • DNA Transposable Elements / genetics*
  • DNA, Circular / genetics
  • Exotoxins / chemistry
  • Exotoxins / genetics
  • Family
  • Female
  • Gene Duplication
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Genome, Bacterial
  • Genomics*
  • Humans
  • Inverted Repeat Sequences / genetics*
  • Leukocidins / chemistry
  • Leukocidins / genetics
  • Male
  • Mutagenesis, Insertional / genetics
  • Polymerase Chain Reaction
  • Prophages / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Staphylococcal Infections / microbiology*
  • Staphylococcal Infections / transmission
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / isolation & purification*
  • Staphylococcus aureus / pathogenicity
  • Virulence Factors / biosynthesis
  • Virulence Factors / genetics

Substances

  • Bacterial Toxins
  • DNA Transposable Elements
  • DNA, Circular
  • Exotoxins
  • Leukocidins
  • Panton-Valentine leukocidin
  • RNA, Messenger
  • Virulence Factors

Grants and funding

This study was supported mainly by personal (TY) money including that obtained from lectures at universities and colleges. This study was also supported partly by reagents and other research materials used in routine research works for Ph. D students (TWW, WH, YI, TT, and YTL) in National Taiwan University College of Medicine and Niigata University Graduate School of Medical and Dental Sciences and for staffs (OEK, WCH, OVP, KKK, ABS, and LJT) in Krasnoyarsk State Medical University, Kaohsiung Medical University, and National Cheng Kung University, and by routine clinical works for staffs (MW and NI) in Kido Hospital. There was no specific funding during this study and authors did not receive a salary for this specific study.