Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

ABSTRACT Transporters belonging to the chromosomally encoded resistance-nodulation-division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria. However, the cotransfer of large gene clusters encoding RND-type pumps from the chromosome to a plasmid appears infrequent, and no pla...

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Autores principales:	Luchao Lv, Miao Wan, Chengzhen Wang, Xun Gao, Qiwen Yang, Sally R. Partridge, Yang Wang, Zhiyong Zong, Yohei Doi, Jianzhong Shen, Peiyao Jia, Qianhua Song, Qianhui Zhang, Jun Yang, Xianhui Huang, Minggui Wang, Jian-Hua Liu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Enterobacteriaceae antimicrobial agents efflux pumps mechanisms of resistance multidrug resistance plasmid-mediated resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/275a9babc0f443eb9dcb6b4e5a071b96
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spelling	oai:doaj.org-article:275a9babc0f443eb9dcb6b4e5a071b962021-11-15T15:57:02ZEmergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>10.1128/mBio.02930-192150-7511https://doaj.org/article/275a9babc0f443eb9dcb6b4e5a071b962020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02930-19https://doaj.org/toc/2150-7511ABSTRACT Transporters belonging to the chromosomally encoded resistance-nodulation-division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria. However, the cotransfer of large gene clusters encoding RND-type pumps from the chromosome to a plasmid appears infrequent, and no plasmid-mediated RND efflux pump gene cluster has yet been found to confer resistance to tigecycline. Here, we identified a novel RND efflux pump gene cluster, designated tmexCD1-toprJ1, on plasmids from five pandrug-resistant Klebsiella pneumoniae isolates of animal origin. TMexCD1-TOprJ1 increased (by 4- to 32-fold) the MICs of tetracyclines (including tigecycline and eravacycline), quinolones, cephalosporins, and aminoglycosides for K. pneumoniae, Escherichia coli, and Salmonella. TMexCD1-TOprJ1 is closely related (64.5% to 77.8% amino acid identity) to the MexCD-OprJ efflux pump encoded on the chromosome of Pseudomonas aeruginosa. In an IncFIA plasmid, pHNAH8I, the tmexCD1-toprJ1 gene cluster lies adjacent to two genes encoding site-specific integrases, which may have been responsible for its acquisition. Expression of TMexCD1-TOprJ1 in E. coli resulted in increased tigecycline efflux and in K. pneumoniae negated the efficacy of tigecycline in an in vivo infection model. Expression of TMexCD1-TOprJ1 reduced the growth of E. coli and Salmonella but not K. pneumoniae. tmexCD1-toprJ1-positive Enterobacteriaceae isolates were rare in humans (0.08%) but more common in chicken fecal (14.3%) and retail meat (3.4%) samples. Plasmid-borne tmexCD1-toprJ1-like gene clusters were identified in sequences in GenBank from Enterobacteriaceae and Pseudomonas strains from multiple continents. The possibility of further global dissemination of the tmexCD1-toprJ1 gene cluster and its analogues in Enterobacteriaceae via plasmids may be an important consideration for public health planning. IMPORTANCE In an era of increasing concerns about antimicrobial resistance, tigecycline is likely to have a critically important role in the treatment of carbapenem-resistant Enterobacteriaceae, the most problematic pathogens in human clinical settings—especially carbapenem-resistant K. pneumoniae. Here, we identified a new plasmid-borne RND-type tigecycline resistance determinant, TMexCD1-TOprJ1, which is widespread among K. pneumoniae isolates from food animals. tmexCD1-toprJ1 appears to have originated from the chromosome of a Pseudomonas species and may have been transferred onto plasmids by adjacent site-specific integrases. Although tmexCD1-toprJ1 still appears to be rare in human clinical isolates, considering the transferability of the tmexCD1-toprJ1 gene cluster and the broad substrate spectrum of TMexCD1-TOprJ1, further dissemination of this mobile tigecycline resistance determinant is possible. Therefore, from a “One Health” perspective, measures are urgently needed to monitor and control its further spread. The current low prevalence in human clinical isolates provides a precious time window to design and implement measures to tackle this.Luchao LvMiao WanChengzhen WangXun GaoQiwen YangSally R. PartridgeYang WangZhiyong ZongYohei DoiJianzhong ShenPeiyao JiaQianhua SongQianhui ZhangJun YangXianhui HuangMinggui WangJian-Hua LiuAmerican Society for MicrobiologyarticleEnterobacteriaceaeantimicrobial agentsefflux pumpsmechanisms of resistancemultidrug resistanceplasmid-mediated resistanceMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Enterobacteriaceae antimicrobial agents efflux pumps mechanisms of resistance multidrug resistance plasmid-mediated resistance Microbiology QR1-502
spellingShingle	Enterobacteriaceae antimicrobial agents efflux pumps mechanisms of resistance multidrug resistance plasmid-mediated resistance Microbiology QR1-502 Luchao Lv Miao Wan Chengzhen Wang Xun Gao Qiwen Yang Sally R. Partridge Yang Wang Zhiyong Zong Yohei Doi Jianzhong Shen Peiyao Jia Qianhua Song Qianhui Zhang Jun Yang Xianhui Huang Minggui Wang Jian-Hua Liu Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
description	ABSTRACT Transporters belonging to the chromosomally encoded resistance-nodulation-division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria. However, the cotransfer of large gene clusters encoding RND-type pumps from the chromosome to a plasmid appears infrequent, and no plasmid-mediated RND efflux pump gene cluster has yet been found to confer resistance to tigecycline. Here, we identified a novel RND efflux pump gene cluster, designated tmexCD1-toprJ1, on plasmids from five pandrug-resistant Klebsiella pneumoniae isolates of animal origin. TMexCD1-TOprJ1 increased (by 4- to 32-fold) the MICs of tetracyclines (including tigecycline and eravacycline), quinolones, cephalosporins, and aminoglycosides for K. pneumoniae, Escherichia coli, and Salmonella. TMexCD1-TOprJ1 is closely related (64.5% to 77.8% amino acid identity) to the MexCD-OprJ efflux pump encoded on the chromosome of Pseudomonas aeruginosa. In an IncFIA plasmid, pHNAH8I, the tmexCD1-toprJ1 gene cluster lies adjacent to two genes encoding site-specific integrases, which may have been responsible for its acquisition. Expression of TMexCD1-TOprJ1 in E. coli resulted in increased tigecycline efflux and in K. pneumoniae negated the efficacy of tigecycline in an in vivo infection model. Expression of TMexCD1-TOprJ1 reduced the growth of E. coli and Salmonella but not K. pneumoniae. tmexCD1-toprJ1-positive Enterobacteriaceae isolates were rare in humans (0.08%) but more common in chicken fecal (14.3%) and retail meat (3.4%) samples. Plasmid-borne tmexCD1-toprJ1-like gene clusters were identified in sequences in GenBank from Enterobacteriaceae and Pseudomonas strains from multiple continents. The possibility of further global dissemination of the tmexCD1-toprJ1 gene cluster and its analogues in Enterobacteriaceae via plasmids may be an important consideration for public health planning. IMPORTANCE In an era of increasing concerns about antimicrobial resistance, tigecycline is likely to have a critically important role in the treatment of carbapenem-resistant Enterobacteriaceae, the most problematic pathogens in human clinical settings—especially carbapenem-resistant K. pneumoniae. Here, we identified a new plasmid-borne RND-type tigecycline resistance determinant, TMexCD1-TOprJ1, which is widespread among K. pneumoniae isolates from food animals. tmexCD1-toprJ1 appears to have originated from the chromosome of a Pseudomonas species and may have been transferred onto plasmids by adjacent site-specific integrases. Although tmexCD1-toprJ1 still appears to be rare in human clinical isolates, considering the transferability of the tmexCD1-toprJ1 gene cluster and the broad substrate spectrum of TMexCD1-TOprJ1, further dissemination of this mobile tigecycline resistance determinant is possible. Therefore, from a “One Health” perspective, measures are urgently needed to monitor and control its further spread. The current low prevalence in human clinical isolates provides a precious time window to design and implement measures to tackle this.
format	article
author	Luchao Lv Miao Wan Chengzhen Wang Xun Gao Qiwen Yang Sally R. Partridge Yang Wang Zhiyong Zong Yohei Doi Jianzhong Shen Peiyao Jia Qianhua Song Qianhui Zhang Jun Yang Xianhui Huang Minggui Wang Jian-Hua Liu
author_facet	Luchao Lv Miao Wan Chengzhen Wang Xun Gao Qiwen Yang Sally R. Partridge Yang Wang Zhiyong Zong Yohei Doi Jianzhong Shen Peiyao Jia Qianhua Song Qianhui Zhang Jun Yang Xianhui Huang Minggui Wang Jian-Hua Liu
author_sort	Luchao Lv
title	Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_short	Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full	Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_fullStr	Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full_unstemmed	Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_sort	emergence of a plasmid-encoded resistance-nodulation-division efflux pump conferring resistance to multiple drugs, including tigecycline, in <named-content content-type="genus-species">klebsiella pneumoniae</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/275a9babc0f443eb9dcb6b4e5a071b96
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Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

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