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

• Published in: Nature microbiology Vol. 4; no. 9; pp. 1457 - 1464
• Main Authors: Sun, Jian, Chen, Chong, Cui, Chao-Yue, Zhang, Yan, Liu, Xiao, Cui, Ze-Hua, Ma, Xiao-Yu, Feng, Youjun, Fang, Liang-Xing, Lian, Xin-Lei, Zhang, Rong-Min, Tang, You-Zhi, Zhang, Kou-Xing, Liu, Han-Mian, Zhuang, Zhi-Hui, Zhou, Shi-Dan, Lv, Jing-Nan, Du, Hong, Huang, Bin, Yu, Fang-You, Mathema, Barun, Kreiswirth, Barry N., Liao, Xiao-Ping, Chen, Liang, Liu, Ya-Hong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2019; Nature Publishing Group
• Subjects: 101/58; 38/23; 38/44; 38/77; 45/22; 45/29; 631/326/22/1434; 631/326/41/1470; 631/326/41/2531; 64/60; 692/308/174; Animal models; Animals; Antibiotics; Biomedical and Life Sciences; Chickens; China - epidemiology; Drug Resistance, Bacterial - genetics; E coli; Environmental Microbiology; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - isolation & purification; Escherichia coli Infections - drug therapy; Escherichia coli Infections - epidemiology; Escherichia coli Infections - microbiology; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Genes, Bacterial; Humans; Infectious Diseases; Letter; Life Sciences; Medical Microbiology; Mice; Microbial Sensitivity Tests; Microbiology; Multidrug resistance; Niches; Parasitology; Plasmids - chemistry; Plasmids - genetics; Strains (organisms); Swine; Tetracyclines; Tetracyclines - metabolism; Tetracyclines - pharmacology; Tigecycline; Tigecycline - metabolism; Tigecycline - pharmacology; Virology; China
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-019-0496-4

Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria 1 . Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection 2 , 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. Plasmid-encoded tet (X) genes from Escherichia coli in China confer high-level tigecycline resistance.