Structural diversity of the ISCR2-mediated rolling-cycle transferable unit carrying tet(X4)

Dejun Liu; Tao Wang; Dongyan Shao; Huangwei Song; Weishuai Zhai; Chengtao Sun; Ying Zhang; Muchen Zhang; Yulin Fu; Rong Zhang; Tao He; Ziquan Lv; Li Bai; Congming Wu; Yuebin Ke; Yang Wang; Zhangqi Shen

doi:10.1016/j.scitotenv.2022.154010

Structural diversity of the ISCR2-mediated rolling-cycle transferable unit carrying tet(X4)

Sci Total Environ. 2022 Jun 20:826:154010. doi: 10.1016/j.scitotenv.2022.154010. Epub 2022 Feb 23.

Authors

Dejun Liu¹, Tao Wang², Dongyan Shao¹, Huangwei Song¹, Weishuai Zhai¹, Chengtao Sun¹, Ying Zhang³, Muchen Zhang¹, Yulin Fu¹, Rong Zhang⁴, Tao He⁵, Ziquan Lv⁶, Li Bai⁷, Congming Wu¹, Yuebin Ke⁶, Yang Wang¹, Zhangqi Shen⁸

Affiliations

¹ College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
² Department of Gastroenterology, the fourth Medical Center of PLA General Hospital, 100048, China.
³ Department of Microbiology, The General Hospital of PLA, Beijing 100853, China.
⁴ The Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang 310009, China.
⁵ Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu 210014, China.
⁶ Key Laboratory of Genetics & Molecular, Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518000, China.
⁷ Key Laboratory of Food Safety Risk Assessment, National Health Commission of the People's Republic of China, China National Center for Food Safety Risk Assessment, Beijing 100022, China.
⁸ College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address: szq@cau.edu.cn.

PMID: 35218833
DOI: 10.1016/j.scitotenv.2022.154010

Abstract

Background: Mobile tigecycline-resistance gene tet(X) variants have emerged as diverse pathogens from animal, human as well as their associated environments, which could potentially threaten public health. The insertion sequence, ISCR2, carries tet(X4) for horizontal transfer by rolling-cycle (RC) transposition. However, the diversity of ISCR2 and tet(X4) isolated from different sources is largely unknown.

Methods: The tet(X4)-carrying isolates were collected from human and livestock in several multiple regions of China. The whole genomic sequences of these isolates were either obtained from NCBI GenBank or determined by Illumina Hiseq 2500 and the MinION platform. The intact transposon region, ISCR2-tet(X4)-ISCR2, observed in a small number of isolates as the reference sequence to construct the transposon phylogeny. The diversity of the genetic environments of all ISCR2-tet(X4) elements were analyzed.

Results: A 2760-bp element encompassing the tet(X4)-hydrolase-encoding gene, catD, located between two ISCR2 elements was highly conserved in all isolates and could form an RC transposable unit (RC-TU). ISCR2 could also capture more resistance genes and formed a larger RC-TU base on RC transposition. However, the ISCR2-mediated RC-TUs were constantly truncated and inserted by other IS elements, indicating frequent recombination events. Of these elements, IS26 disrupted both the upstream and downstream ISCR2-mediated RC-TUs, indicating that IS26 captured tet(X4), thus leading to a wider spread of tet(X4).

Conclusions: These results confirmed the critical role of ISCR2 for dissemination and co-transmission of tet(X4) and other resistance genes. More effort is needed to monitor the variation tendencies of tet(X4)-carrying mobile elements and determine the driving factors for disseminating transferable tigecycline resistance.

Keywords: ISCR2; Rolling cycle transposition; Tet(X4); Tigecycline.

MeSH terms

Animals
Anti-Bacterial Agents*
Escherichia coli* / genetics
Microbial Sensitivity Tests
Plasmids
Tigecycline

Substances

Anti-Bacterial Agents
Tigecycline