IS26-mediated plasmid reshuffling results in convergence of toxin–antitoxin systems but loss of resistance genes in XDR Klebsiella pneumoniae from a chronic infection

Ting L. Luo, Brendan W. Corey, Erik Snesrud, Alina Iovleva, Christi L. McElheny, Lan N. Preston, Yoon I. Kwak, Jason W. Bennett, Yohei Doi, Patrick T. McGann, Francois Lebreton

Research output: Contribution to journalArticlepeer-review

Abstract

Carbapenem-resistant Enterobacterales pose an urgent threat to human health worldwide. Klebsiella pneumoniae sequence type (ST) 14, initially identified in the Middle East and South-Asia and co-harbouring the carbapenemase genes blaOXA-232 and blaNDM-1, is now emerging globally. One such strain was detected in the USA in 2013 from a patient initially treated in India that also carried armA, a 16S rRNA methyltransferase that confers resistance to all clinically relevant aminoglyco-sides. Genetic and phenotypic changes were observed in 14 serial isolates collected from this chronically infected patient. The index isolate carried five plasmids, including an IncFIB–IncHI1B (harbouring armA and blaNDM-1 ), an IncFIA (blaCTX-M-15 ) and a ColE-like (blaOXA-232 ), and was extensively resistant to antibiotics. Four years later, a subsequent isolate had accumu-lated 34 variants, including a loss-of-function mutation in romA, resulting in tigecycline non-susceptibility. Importantly, this isolate now only carried two plasmids, including a large mosaic molecule made of fragments, all harbouring distinct toxin–antitoxin systems, from three of the canonical plasmids. Of the original acquired antibiotic resistance genes, this isolate only retained blaCTX-M-15, and as a result susceptibility to the carbapenems and amikacin was restored. Long-read sequencing of a subset of five representative isolates, collected between 2013 and 2017, allowed for the elucidation of the complex plasmid patterns and revealed the role of IS26-mediated plasmid reshuffling in the evolution of this clone. Such investigations of the mechanisms underlying plasmid stability, together with global and local surveillance programmes, are key to a better understanding of plasmid host range and dissemination.

Original languageEnglish
Article number000892
JournalMicrobial genomics
Volume8
Issue number9
DOIs
Publication statusPublished - 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Microbiology
  • Molecular Biology
  • Genetics

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