1. Identification of multiple transfer units and novel subtypes of tmexCD-toprJ gene clusters in clinical carbapenem-resistant Enterobacter cloacae and Klebsiella oxytoca.
- Author
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Sun, Shijun, Wang, Qi, Jin, Longyang, Guo, Yifan, Yin, Yuyao, Wang, Ruobing, Bi, Lei, Zhang, Renfei, Han, Yungang, and Wang, Hui
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ENTEROBACTER cloacae ,KLEBSIELLA oxytoca ,COVID-19 ,GENE clusters ,INTEGRASES ,TIGECYCLINE ,KLEBSIELLA ,ANTIBIOTICS ,RESEARCH ,BIOLOGICAL evolution ,GRAM-negative bacteria ,EVALUATION research ,HYDROLASES ,COMPARATIVE studies ,GENES ,RESEARCH funding ,CARBAPENEMS ,MICROBIAL sensitivity tests ,PHARMACODYNAMICS - Abstract
Objectives: Tigecycline is a last-resort antibiotic used to treat lethal infections caused by carbapenem-resistant Enterobacterales; however, plasmid-borne tigecycline resistance tmexCD-toprJ gene clusters can confer tigecycline resistance. The aim of the study was to identify novel subtypes and the spread of tmexCD-toprJ.Methods: Five non-duplicate isolates of different species, carrying tmexCD-toprJ gene clusters or novel subtypes, were isolated from patients across China between November 2018 and June 2019. WGS was performed using Illumina and Nanopore platforms. A phylogenetic tree was constructed using a dataset of 77 sequences carrying the tmexCD-toprJ gene clusters, 72 of which were downloaded from NCBI with a blastn identity cut-off of 95%.Results: We detected six different transfer units and two novel subtypes (tmexC1D1.2-toprJ1 and tmexC2D2.2-toprJ2) of the tmexCD-toprJ gene clusters. Among the six transfer units, three were mediated by IS26, while the rest were presumably mediated by Tn5393, hypothetical integrases (xerD-hp clusters-umuC-integrases-tnfxB2-tmexC2D2-toprJ2-umuC) and hypothetical units (hp-hp-hp-tnfxB2-tmexC2D2.2-toprJ2-ΔTn5393-Tn6292). Moreover, two tmexCD-toprJ-like gene clusters co-located on the same plasmid with blaNDM in five isolates. Phylogenetic analysis revealed that tmexCD-toprJ gene clusters may have originated in Pseudomonas spp., being mainly distributed in Pseudomonas spp. and Klebsiella spp. (64/77). Most tmexCD-toprJ gene clusters in Enterobacterales were located on plasmids, indicating that the gene clusters have a high inter-species transfer risk after transfer to Enterobacterales.Conclusions: In summary, to the best of our knowledge, this is the first report of tmexCD-toprJ gene clusters being isolated from Enterobacter cloacae and Klebsiella oxytoca, revealing that these multiple transfer units should be further studied because of their clinical significance. [ABSTRACT FROM AUTHOR]- Published
- 2022
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