TY - JOUR
T1 - IS26-mediated plasmid reshuffling results in convergence of toxin–antitoxin systems but loss of resistance genes in XDR Klebsiella pneumoniae from a chronic infection
AU - Luo, Ting L.
AU - Corey, Brendan W.
AU - Snesrud, Erik
AU - Iovleva, Alina
AU - McElheny, Christi L.
AU - Preston, Lan N.
AU - Kwak, Yoon I.
AU - Bennett, Jason W.
AU - Doi, Yohei
AU - McGann, Patrick T.
AU - Lebreton, Francois
N1 - Funding Information:
This study was funded by the US Army Medical Command and the Defense Medical Research and Development Program. A.I. was supported through Physician Scientist Incubator Program at the University of Pittsburgh sponsored by the Burrows Wellcome Fund and an appointee of institutional training grant from the National Institutes of Health (KL2TR001856). Y.D. was supported by research grants from the National Institutes of Health (R01AI104895, R21AI151362, R21AI035522).
Funding Information:
This study was funded by the US Army Medical Command and the Defense Medical Research and Development Program. A.I. was supported through Physician Scientist Incubator Program at the University of Pittsburgh sponsored by the Burrows Wellcome Fund and an appointee of institutional training grant from the National Institutes of Health (KL2TR001856). Y.D. was supported by research grants from the National Institutes of Health (R01AI104895, R21AI151362, R21AI035522). Acknowledgements The manuscript has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense.
Publisher Copyright:
© 2022 The Authors.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - CRE
KW - NDM
KW - OXA-232
KW - ST14
KW - mosaic plasmids
KW - within-host evolution
UR - http://www.scopus.com/inward/record.url?scp=85139135234&partnerID=8YFLogxK
U2 - 10.1099/mgen.0.000892
DO - 10.1099/mgen.0.000892
M3 - Article
C2 - 36169644
AN - SCOPUS:85139135234
SN - 2057-5858
VL - 8
JO - Microbial Genomics
JF - Microbial Genomics
IS - 9
M1 - 000892
ER -