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Volume 8, Issue 9

IS-mediated plasmid reshuffling results in convergence of toxin–antitoxin systems but loss of resistance genes in XDR from a chronic infection Open Access

Abstract

Carbapenem-resistant pose an urgent threat to human health worldwide. sequence type (ST) 14, initially identified in the Middle East and South-Asia and co-harbouring the carbapenemase genes and is now emerging globally. One such strain was detected in the USA in 2013 from a patient initially treated in India that also carried , a 16S rRNA methyltransferase that confers resistance to all clinically relevant aminoglycosides. 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 and ), an IncFIA ( ) and a ColE-like ( ), and was extensively resistant to antibiotics. Four years later, a subsequent isolate had accumulated 34 variants, including a loss-of-function mutation in , 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 , 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 IS-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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): CRE , mosaic plasmids , NDM , OXA-232 , ST14 and within-host evolution
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2022-09-28
2024-04-25
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IS26-mediated plasmid reshuffling results in convergence of toxin–antitoxin systems but loss of resistance genes in XDR Klebsiella pneumoniae from a chronic infection
M Gen 8, 000892 (2022); https://doi.org/10.1099/mgen.0.000892
/content/journal/mgen/10.1099/mgen.0.000892
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