Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniae

Tigecycline is considered one of the last-resort antimicrobials for carbapenem-resistant K. pneumoniae. Plasmid-mediated tigecycline resistance remains largely unclear. Here, by utilizing whole genome sequencing, we report a plasmid-mediated tigecycline resistance mechanism, a 6,489 bp Resistance-no...

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Main Authors: Shijun Sun, Hua Gao, Yudong Liu, Longyang Jin, Ruobing Wang, Xiaojuan Wang, Qi Wang, Yuyao Yin, Yawei Zhang, Hui Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1768805
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author Shijun Sun
Hua Gao
Yudong Liu
Longyang Jin
Ruobing Wang
Xiaojuan Wang
Qi Wang
Yuyao Yin
Yawei Zhang
Hui Wang
author_facet Shijun Sun
Hua Gao
Yudong Liu
Longyang Jin
Ruobing Wang
Xiaojuan Wang
Qi Wang
Yuyao Yin
Yawei Zhang
Hui Wang
author_sort Shijun Sun
collection DOAJ
description Tigecycline is considered one of the last-resort antimicrobials for carbapenem-resistant K. pneumoniae. Plasmid-mediated tigecycline resistance remains largely unclear. Here, by utilizing whole genome sequencing, we report a plasmid-mediated tigecycline resistance mechanism, a 6,489 bp Resistance-nodulation-division family (RND) efflux pump (tmexCD1-toprJ1 pump), that confers transferable tigecycline resistance in K pneumoniae isolated from patients and chickens. In addition, we identified high prevalence of the plasmids co-harbouring both tmexCD1-toprJ1 pump and mcr (tmexCD1-mcr co-harbouring plasmid) from human in our nationwide collection. Even worse, the tmexCD1-toprJ1 and mcr co-harbouring plasmid was also co-existed with blaNDM-harbouring IncX3 plasmid in the same host, resulting in pandrug resistance. Phylogenetic analysis suggested that the plasmid-borne tmexCD1-toprJ1 originated from the chromosome of Aeromonas spp. through Tn5393-mediating translocation. Both plasmid-harbored tmexCD1-toprJ1 gene and mcr-8 likely originated from animal isolates and then spread to human. Our findings highlight a substantial threat of tmexCD1-toprJ1-mcr8 co-harbouring IncFIA/IncFII plasmid to public health due to their mobile resistance to both tigecycline and colistin, emphasizing an urgent need for further global surveillance on this plasmid.
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spelling doaj-art-4d79ef2d01cf4d7bb5beef5037f5a9bd2025-08-20T02:12:15ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01911102111310.1080/22221751.2020.1768805Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniaeShijun Sun0Hua Gao1Yudong Liu2Longyang Jin3Ruobing Wang4Xiaojuan Wang5Qi Wang6Yuyao Yin7Yawei Zhang8Hui Wang9Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaTigecycline is considered one of the last-resort antimicrobials for carbapenem-resistant K. pneumoniae. Plasmid-mediated tigecycline resistance remains largely unclear. Here, by utilizing whole genome sequencing, we report a plasmid-mediated tigecycline resistance mechanism, a 6,489 bp Resistance-nodulation-division family (RND) efflux pump (tmexCD1-toprJ1 pump), that confers transferable tigecycline resistance in K pneumoniae isolated from patients and chickens. In addition, we identified high prevalence of the plasmids co-harbouring both tmexCD1-toprJ1 pump and mcr (tmexCD1-mcr co-harbouring plasmid) from human in our nationwide collection. Even worse, the tmexCD1-toprJ1 and mcr co-harbouring plasmid was also co-existed with blaNDM-harbouring IncX3 plasmid in the same host, resulting in pandrug resistance. Phylogenetic analysis suggested that the plasmid-borne tmexCD1-toprJ1 originated from the chromosome of Aeromonas spp. through Tn5393-mediating translocation. Both plasmid-harbored tmexCD1-toprJ1 gene and mcr-8 likely originated from animal isolates and then spread to human. Our findings highlight a substantial threat of tmexCD1-toprJ1-mcr8 co-harbouring IncFIA/IncFII plasmid to public health due to their mobile resistance to both tigecycline and colistin, emphasizing an urgent need for further global surveillance on this plasmid.https://www.tandfonline.com/doi/10.1080/22221751.2020.1768805Plasmid-mediated tigecycline-resistant K. pneumoniaetmexCD1-toprJ1 efflux pumpmcr-8·5tmexCD1-mcr co-harbouring plasmidCRKP
spellingShingle Shijun Sun
Hua Gao
Yudong Liu
Longyang Jin
Ruobing Wang
Xiaojuan Wang
Qi Wang
Yuyao Yin
Yawei Zhang
Hui Wang
Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniae
Emerging Microbes and Infections
Plasmid-mediated tigecycline-resistant K. pneumoniae
tmexCD1-toprJ1 efflux pump
mcr-8·5
tmexCD1-mcr co-harbouring plasmid
CRKP
title Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniae
title_full Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniae
title_fullStr Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniae
title_full_unstemmed Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniae
title_short Co-existence of a novel plasmid-mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in Klebsiella pneumoniae
title_sort co existence of a novel plasmid mediated efflux pump with colistin resistance gene mcr in one plasmid confers transferable multidrug resistance in klebsiella pneumoniae
topic Plasmid-mediated tigecycline-resistant K. pneumoniae
tmexCD1-toprJ1 efflux pump
mcr-8·5
tmexCD1-mcr co-harbouring plasmid
CRKP
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1768805
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