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Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans

文献类型： 外文期刊

作者： He, Tao 1 ; Wang, Ran 1 ; Liu, Dejun 2 ; Walsh, Timothy R. 2 ; Zhang, Rong 4 ; Lv, Yuan 5 ; Ke, Yuebin 6 ; Ji, Quanjiang; 1 ;

作者机构： 1.Jiangsu Acad Agr Sci, Inst Food Safety & Nutr,Minist Agr & Rural Affair, Key Lab Control Technol & Stand Agroprod Safety &, Jiangsu Key Lab Food Qual & Safety,State Key Lab, Nanjing, Jiangsu, Peoples R China

2.China Agr Univ, Coll Vet Med, Beijing Adv Innovat Ctr Food Nutr & Human Hlth, Beijing, Peoples R China

3.Inst Infect & Immun, Dept Med Microbiol & Infect Dis, Cardiff, S Glam, Wales

4.Zhejiang Univ, Affiliated Hosp 2, Hangzhou, Zhejiang, Peoples R China

5.Peking Univ, Hosp 1, Inst Clin Pharmacol, Beijing, Peoples R China

6.Shenzhen Ctr Dis Control & Prevent, Key Lab Mol Epidemiol Shenzhen, Shenzhen, Peoples R China

7.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai, Peoples R China

8.China Agr Univ, Coll Vet Med, Beijing Key Lab Detect Technol Anim Derived Food, Beijing, Peoples R China

期刊名称：NATURE MICROBIOLOGY （ 影响因子：17.745； 五年影响因子：18.905 ）

ISSN： 2058-5276

年卷期： 2019 年 4 卷 9 期

页码：

收录情况： SCI

摘要： Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria.tet(X) has been shown to encode a flavin-dependent monooxygenase that modifies tigecycline(1,2). Here, we report two unique mobile tigecycline-resistance genes, tet(X3) and tet(X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet(X3) and tet(X4) increase (by 64-128-fold) the tigecycline minimal inhibitory concentration values for Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. In addition, both Tet(X3) (A. baumannii) and Tet(X4) (E. coli) significantly compromise tigecycline in in vivo infection models. Both tet(X3) and tet(X4) are adjacent to insertion sequence ISVsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet(X3) and tet(X4) are globally present in clinical bacteria-even in the same bacteria as bla(NDM-1), resulting in resistance to both tigecycline and carbapenems. Our findings suggest that both the surveillance of tet(X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention.

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