IS26 mediated antimicrobial resistance gene shuffling from the chromosome to a mosaic conjugative FII plasmid

Plasmid. 2018 Nov:100:22-30. doi: 10.1016/j.plasmid.2018.10.001. Epub 2018 Oct 16.

Abstract

In the present study we report the identification of a sul3-associated class 1 integron containing the dfrA12-orfF-aadA2-cmlA1-aadA1-qacH array embedded in a Tn21-derived element that is part of a conjugative FII plasmid named pST1007-1A. The plasmid was identified in the Salmonella Typhimurium strain ST1007, a member of a clinically relevant clonal MDR lineage diffuse in Italy. ST1007 exhibited resistance to ampicillin, chloramphenicol, streptomycin, sulphamethoxazole, tetracycline and trimethoprim encoded by blaTEM-1, cmlA1, (aadA1, aadA2, strAB), (sul2, sul3), tet(B) and dfrA12 genes, respectively. Apart from pST1007-1A, ST1007 also harbours two chromosome-integrated resistance units RU1 (blaTEM-1-sul2-strAB) and RU2 (tet(B)), flanked by IS26 elements. RU1 and RU2 were able to move as translocatable units, respectively TU1 and TU2, and integrate via IS26 mediated recombination into pST1007-1A. A family of conjugative plasmids, harbouring different sets of antimicrobial resistance genes (ARG) was then generated: pST1007-1B (dfrA12-aadA2-cmlA1-aadA1-sul3- tet(B)), pST1007-1C (dfrA12-aadA2-cmlA1-aadA1-sul3-blaTEM-1-sul2-strAB), pST1007-1D (blaTEM-1-sul2-strAB), pST1007-1E (tet(B)) and pST1007-1F (dfrA12-aadA2-cmlA1-aadA1-sul3- tet(B) -blaTEM-1-sul2-strAB). pST1007-1A is also a mosaic plasmid containing two distinct DNA fragments acquired from I1 plasmids through recombination within the repA4, rfsF and repeat-3 sites. This study further highlights the role played by IS26 in intracellular ARGs shuffling. Moreover, attention has been focused on recombination hot spots that might play a key role in generating mosaic plasmids.

Keywords: IS26; Mosaic Plasmid; Multidrug resistance; Tn21-derived.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Chromosome Mapping
  • Conjugation, Genetic
  • DNA Replication
  • DNA Transposable Elements
  • Drug Resistance, Bacterial / genetics*
  • Genome, Bacterial*
  • Integrons*
  • Operon
  • Plasmids / chemistry*
  • Plasmids / metabolism
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / metabolism

Substances

  • Anti-Bacterial Agents
  • DNA Transposable Elements