Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in Klebsiella pneumoniae.

MBio
Luchao LvJian-Hua Liu

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...Continue Reading

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Citations

Jul 11, 2020·Journal of Environmental Science and Health. Part C, Toxicology and Carcinogenesis·Prabin ShresthaTit-Yee Wong
Feb 4, 2021·The Journal of Antimicrobial Chemotherapy·Ursula TheuretzbacherEvelina Tacconelli
Feb 9, 2021·BioMed Research International·Madubuike Umunna AnyanwuVincent Shodeinde Shoyinka
Mar 12, 2021·Journal of Medical Microbiology·Aki HirabayashiMasato Suzuki
Apr 6, 2021·Frontiers in Cellular and Infection Microbiology·Ting YuDongsheng Zhou
May 26, 2021·Expert Review of Anti-infective Therapy·Ilias KaraiskosHelen Giamarellou
Nov 13, 2021·Frontiers in Cellular and Infection Microbiology·Yanling LiuLingbing Zeng

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Datasets Mentioned

BETA
MG736312
MK262712.1
QFMD01000298
QWIX01000043.1
MK347425

Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

GraphPad
ClustalX
GraphPad Prism
ISfinder Antibiotic Resistance Annotator ( MARA )
Unicycler
MEGA X

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