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已发表论文
从“同一健康”视角看克雷伯菌属中 tmexCD-toprJ 的质粒骨架偏好和进化适应
Authors Jiang X, Liu F, Chai J, Li X, Li Y, Fu S, Li Y
Received 12 December 2025
Accepted for publication 2 February 2026
Published 12 February 2026 Volume 2026:19 585632
DOI https://doi.org/10.2147/IDR.S585632
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Hemant Joshi
Xinli Jiang,1,* Fumei Liu,1,* Jiatong Chai,1 Xingrong Li,1 Yumei Li,1 Shiyu Fu,1 Yirong Li1– 3
1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, People’s Republic of China; 3Wuhan Research Center for Infectious Diseases and Tumors of the Chinese Academy of Medical Sciences, Wuhan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yirong Li, Email liyirong838@163.com
Background: Antimicrobial resistance (AMR) poses a critical One Health challenge, linking human, animal, and environmental health through the movement of multidrug-resistant (MDR) bacteria and resistance determinants. The tmexCD-toprJ gene cluster, an efflux pump conferring high-level resistance to tigecycline and eravacycline. However, its plasmid backbone preferences and evolutionary trajectories in Klebsiella spp. remain insufficiently characterized.
Methods: This study investigated the plasmid backbone preference and evolutionary characteristics of tmexCD-toprJ-harboring plasmids in Klebsiella spp. using whole-genome sequencing of three clinical strains carrying tmexCD-toprJ collected from 2018 to 2023. Conjugation assays, comparative genomics, and global epidemiological analysis were performed to assess plasmid mobility, genetic context, and evolutionary direction under the One Health framework.
Results: All three isolates (K7, K36, and K307) exhibited MDR and harbored major resistance genes, including blaIMP-4, mcr-1.1, and blaNDM-1, respectively. The plasmid from K36 was transferable to EC600 (frequency, 10− 7), confirming cross-species mobility. Global database analysis revealed that tmexCD-toprJ-positive Klebsiella spp. isolates (n=92) originated mainly from humans (59.8%), followed by animals (37.0%) and environments (3.3%). Phylogenetic and plasmid analyses the tmexCD1-toprJ1 variant was mainly associated with these hybrid plasmids, frequently co-localizing with sul1, qnrB, and strA/B to form stable “tigecycline–aminoglycoside–sulfonamide” co-resistance modules. In contrast, tmexCD2-toprJ2 was more often inserted into classical resistant plasmids.
Conclusion: These findings demonstrate that tmexCD-toprJ has evolved as a highly mobile resistance determinant within Klebsiella spp. disseminating across the human–animal–environment interface via hybrid plasmids and horizontal gene transfer. This underscores the urgent need for integrated One Health surveillance and containment strategies to mitigate plasmid-mediated multidrug resistance and its global public health impact.
Keywords: tmexCD-toprJ, Klebsiella spp, one health, horizontal gene transfer, hybrid plasmids
1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, People’s Republic of China; 3Wuhan Research Center for Infectious Diseases and Tumors of the Chinese Academy of Medical Sciences, Wuhan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yirong Li, Email liyirong838@163.com
Background: Antimicrobial resistance (AMR) poses a critical One Health challenge, linking human, animal, and environmental health through the movement of multidrug-resistant (MDR) bacteria and resistance determinants. The tmexCD-toprJ gene cluster, an efflux pump conferring high-level resistance to tigecycline and eravacycline. However, its plasmid backbone preferences and evolutionary trajectories in Klebsiella spp. remain insufficiently characterized.
Methods: This study investigated the plasmid backbone preference and evolutionary characteristics of tmexCD-toprJ-harboring plasmids in Klebsiella spp. using whole-genome sequencing of three clinical strains carrying tmexCD-toprJ collected from 2018 to 2023. Conjugation assays, comparative genomics, and global epidemiological analysis were performed to assess plasmid mobility, genetic context, and evolutionary direction under the One Health framework.
Results: All three isolates (K7, K36, and K307) exhibited MDR and harbored major resistance genes, including blaIMP-4, mcr-1.1, and blaNDM-1, respectively. The plasmid from K36 was transferable to EC600 (frequency, 10− 7), confirming cross-species mobility. Global database analysis revealed that tmexCD-toprJ-positive Klebsiella spp. isolates (n=92) originated mainly from humans (59.8%), followed by animals (37.0%) and environments (3.3%). Phylogenetic and plasmid analyses the tmexCD1-toprJ1 variant was mainly associated with these hybrid plasmids, frequently co-localizing with sul1, qnrB, and strA/B to form stable “tigecycline–aminoglycoside–sulfonamide” co-resistance modules. In contrast, tmexCD2-toprJ2 was more often inserted into classical resistant plasmids.
Conclusion: These findings demonstrate that tmexCD-toprJ has evolved as a highly mobile resistance determinant within Klebsiella spp. disseminating across the human–animal–environment interface via hybrid plasmids and horizontal gene transfer. This underscores the urgent need for integrated One Health surveillance and containment strategies to mitigate plasmid-mediated multidrug resistance and its global public health impact.
Keywords: tmexCD-toprJ, Klebsiella spp, one health, horizontal gene transfer, hybrid plasmids