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.

• Authors: Jian Sun, Chong Chen, Chao-Yue Cui, Yan Zhang, Xiao Liu, Ze-Hua Cui, Xiao-Yu Ma, Youjun Feng, Liang-Xing Fang, Xin-Lei Lian, Rong-Min Zhang, You-Zhi Tang, Kou-Xing Zhang, Han-Mian Liu, Zhi-Hui Zhuang, Shi-Dan Zhou, Jing-Nan Lv, Hong Du, Bin Huang, Fang-You Yu, Barun Mathema, Barry N Kreiswirth, Xiao-Ping Liao, Liang Chen, Ya-Hong Liu
• Journal: Nature microbiology (Nat Microbiol) Vol. 4 Issue 9 Pg. 1457-1464 (09 2019) ISSN: 2058-5276 [Electronic] England
• PMID: 31235960 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Escherichia coli Proteins
• Tetracyclines
• Tigecycline

Topics

• Animals
• Chickens
• China (epidemiology)
• Drug Resistance, Bacterial (genetics)
• Environmental Microbiology
• Escherichia coli (drug effects, genetics, isolation & purification)
• Escherichia coli Infections (drug therapy, epidemiology, microbiology)
• Escherichia coli Proteins (genetics, metabolism)
• Genes, Bacterial
• Humans
• Mice
• Microbial Sensitivity Tests
• Plasmids (chemistry, genetics)
• Swine
• Tetracyclines (metabolism, pharmacology)
• Tigecycline (metabolism, pharmacology)