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Plasmid-encoded tet(X) genes that confer high-level tigecycline resistance in Escherichia coli.

Abstract：

:Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria1. Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection2,3. Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics.

journal_name

Nat Microbiol

journal_title

Nature microbiology

authors

Sun J,Chen C,Cui CY,Zhang Y,Liu X,Cui ZH,Ma XY,Feng Y,Fang LX,Lian XL,Zhang RM,Tang YZ,Zhang KX,Liu HM,Zhuang ZH,Zhou SD,Lv JN,Du H,Huang B,Yu FY,Mathema B,Kreiswirth BN,Liao XP,Chen L,Liu YH

doi

10.1038/s41564-019-0496-4

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

1457-1464

issue

9

issn

2058-5276

pii

10.1038/s41564-019-0496-4

journal_volume

4

pub_type

杂志文章

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