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

Author:

Lv Luchao12,Wan Miao12,Wang Chengzhen12,Gao Xun12,Yang Qiwen3,Partridge Sally R.4ORCID,Wang Yang5,Zong Zhiyong6,Doi Yohei78,Shen Jianzhong5,Jia Peiyao3,Song Qianhua1,Zhang Qianhui1,Yang Jun12,Huang Xianhui12,Wang Minggui9,Liu Jian-Hua12ORCID

Affiliation:

1. College of Veterinary Medicine, National Risk Assessment Laboratory for Antimicrobial Resistance of Microorganisms in Animals, Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China

2. Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China

3. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

4. Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney, Westmead Hospital, Sydney, Australia

5. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China

6. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China

7. Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

8. Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

9. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China

Abstract

In an era of increasing concerns about antimicrobial resistance, tigecycline is likely to have a critically important role in the treatment of carbapenem-resistant Enterobacteriaceae , the most problematic pathogens in human clinical settings—especially carbapenem-resistant K. pneumoniae . Here, we identified a new plasmid-borne RND-type tigecycline resistance determinant, TMexCD1-TOprJ1, which is widespread among K. pneumoniae isolates from food animals. tmexCD1-toprJ1 appears to have originated from the chromosome of a Pseudomonas species and may have been transferred onto plasmids by adjacent site-specific integrases. Although tmexCD1-toprJ1 still appears to be rare in human clinical isolates, considering the transferability of the tmexCD1-toprJ1 gene cluster and the broad substrate spectrum of TMexCD1-TOprJ1, further dissemination of this mobile tigecycline resistance determinant is possible. Therefore, from a “One Health” perspective, measures are urgently needed to monitor and control its further spread. The current low prevalence in human clinical isolates provides a precious time window to design and implement measures to tackle this.

Funder

National Natural Science Foundation of China

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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