Complete Nucleotide Sequence of a Novel Plasmid Bearing the High-Level Tigecycline Resistance Gene tet (X4)

Abstract

We reported the complete nucleotide sequence of a tet(X4)-carrying plasmid, pSTB20-1T, from a tigecycline-resistant Escherichia coli isolate in China. Sequence analysis indicated that pSTB20-1T contains a hybrid plasmid backbone and a tet(X4)-containing multidrug resistance region, likely originated through recombination of multiple plasmids. tet(X4) was flanked by two ISCR2, which may be responsible for tet(X4) mobilization. The occurrence and transmission of this novel hybrid plasmid may exacerbate the spread of the clinically significant tet(X4) gene.

The integrase of genomic island GIsul2 mediates the mobilization of GIsul2 and ISCR-related element CR2-sul2 unit through site-specific recombination

“…These CR2- sul2 units are therefore recognized as vectors of dissemination of antibiotic resistance in environmental bacteria and important clinical pathogens such as Vibrio spp., Pseudoalteromonas spp., Salmonella enterica, S. flexneri , and A. baumannii (Beaber et al, 2002 ; Toleman et al, 2006a ; Yau et al, 2010 ; Leclercq et al, 2016 ; Harmer et al, 2017 ; Xu et al, 2017 ; Shi et al, 2019 ; Wüthrich et al, 2019 ). Especially, plasmid-borne IS CR2 carrying the high-level tigecycline resistance gene tet(X) has emerged in E. coli (Fang et al, 2019 ; He et al, 2019 ; Sun et al, 2019 ), which hints that we should pay close attention to the rise of this element. Interestingly, the boundaries of these transposons have been predicted to lie 119 bp upstream of the rcr gene and 304 bp upstream of sul2 (Leclercq et al, 2016 ), which correspond to the middle of the core recombination region of attLR , and the 3′-end of attR , respectively.…”

“…The first common region (CR) element, CR1, was discovered in the 3′-conserved segment (3′-CS) of some class 1 integrons, where it is associated with antibiotic resistance genes not embedded in gene cassettes and is usually found between partial duplications of the 3′-CS (Stokes et al, 1993 ; Partridge and Hall, 2003 ). Other CR elements were later identified in numerous bacteria, especially in Gram-negative pathogens, and are frequently linked to diverse ARGs (Partridge and Hall, 2003 ; Toleman et al, 2006a ; Schleinitz et al, 2010 ; Fang et al, 2019 ). CR2 is found downstream of the sul2 gene in a head-to-head organization with a truncated glmM gene in between, a structure found at the 3′ end of GI sul2 , and hereafter referred to as the CR2- sul2 unit ( Figure 1 ).…”

“…More commonly, CR2- sul2 units carry various other ARGs in between and locate on other MGEs. Recently, CR2 was also reported to likely contribute to the mobilization of the high-level tigecycline resistance gene tet (X) in Escherichia coli (Fang et al, 2019 ; He et al, 2019 ; Sun et al, 2019 ). CR elements are proposed to move by a process called rolling-circle replication because of the distant similarity of their encoded gene to the transposases of the IS 91 family insertion sequences, known to promote their own spread through this mechanism (Toleman et al, 2006b ).…”

Development of a Multiplex Real-Time PCR Assay for Rapid Detection of Tigecycline Resistance Gene tet (X) Variants from Bacterial, Fecal, and Environmental Samples

“…Since the first report of plasmid-mediated tigecycline resistance genes tet(X3) and tet(X4) a few months ago, there have already been a number of follow-up reports (10,(15)(16)(17)(18). Recently, a novel plasmid-mediated tigecycline resistance gene, tet(X5) variant, was reported in Acinetobacter baumannii in a clinic (11).…”