Identification of TMexCD-TOprJ-producing carbapenem-resistant Gram-negative bacteria from hospital sewage

Jie Zhu; Jingnan Lv; Zhichen Zhu; Tao Wang; Xiaofang Xie; Haifang Zhang; Liang Chen; Hong Du

doi:10.1016/j.drup.2023.100989

Identification of TMexCD-TOprJ-producing carbapenem-resistant Gram-negative bacteria from hospital sewage

Drug Resist Updat. 2023 Sep:70:100989. doi: 10.1016/j.drup.2023.100989. Epub 2023 Jul 13.

Authors

Jie Zhu¹, Jingnan Lv², Zhichen Zhu¹, Tao Wang¹, Xiaofang Xie¹, Haifang Zhang¹, Liang Chen³, Hong Du⁴

Affiliations

¹ Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
² Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China; MOE Key Laboratory of Geriatric Diseases and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, PR China.
³ Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA; Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA.
⁴ Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China; MOE Key Laboratory of Geriatric Diseases and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, PR China. Electronic address: hong_du@126.com.

PMID: 37480594
DOI: 10.1016/j.drup.2023.100989

Abstract

Carbapenems and tigecycline are crucial antimicrobials for the treatment of gram-negative bacteria infections. Recently, a novel resistance-nodulation-division (RND) efflux pump gene cluster, tmexCD-toprJ, which confers resistance to tigecycline, has been discovered in animals and clinical isolates. It was reported that hospital sewage could act as a reservoir for gram-negative bacteria with high antimicrobial resistance genes. In this study, we analyzed 84 isolates of carbapenem-resistant gram-negative bacteria (CR-GNB) from hospital sewage, and identified five isolates of TMexCD-ToprJ-producing CR-GNB, including one Raoultella ornithinolytica isolate and four Pseudomonas spp. isolates. All these five isolates carried at least one carbapenem resistance gene and were resistant to multiple antibiotics. Multiple tmexCD-toprJ clusters were detected, including tmexC2D2-toprJ2, tmexC3D3-toprJ3, tmexC3.2D3.3-toprJ1b and tmexC3.2D3-toprJ1b. Among these clusters, the genetic construct of tmexC3.2D3-toprJ1b showed 2-fold higher minimum inhibitory concentration (MIC) of tigecycline than other three variants. In addition, it was found that the tmexCD-toprJ gene cluster was originated from Pseudomonas spp. and mainly located on Tn6855 variants inserted in the same umuC-like genes on chromosomes and plasmids. This unit co-localized with bla_IMP or bla_VIM on IncHI5-, Inc_pJBCL41- and Inc_pSTY-type plasmids in the five isolates of TMCR-GNB. The IncHI5- and Inc_pSTY-type plasmids had the ability to conjugal transfer to E. coli J53 and P. aeruginosa PAO1, highlighting the potential risk of transfer of tmexCD-toprJ from Pseudomonas spp. to Enterobacterales. Importantly, genomic analysis showed that similar tmexCD-toprJ-harboring IncHI5 plasmids were also detected in human samples, suggesting transmission between environmental and human sectors. The emergence of TMCR-GNB from hospital sewage underscores the need for ongoing surveillance of antimicrobial resistance genes, particularly the novel resistance genes such as the tmexCD-toprJ gene clusters in the wastewater environment.

Keywords: Hospital sewage; Pseudomonas spp.; Raoultella ornithinolytica; Tigecycline; tmexCD-toprJ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Carbapenems* / pharmacology
Escherichia coli
Gram-Negative Bacteria / genetics
Hospitals
Humans
Microbial Sensitivity Tests
Pseudomonas aeruginosa
Sewage*
Tigecycline
beta-Lactamases / genetics

Substances

Carbapenems
Sewage
Tigecycline
Anti-Bacterial Agents
beta-Lactamases