Dataset Information

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.

SUBMITTER: Fang LX

PROVIDER: S-EPMC6811429 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Fang Liang-Xing LX Chen Chong C Yu Dong-Ling DL Sun Ruan-Yang RY Cui Chao-Yue CY Chen Liang L Liao Xiao-Ping XP Liu Ya-Hong YH Sun Jian J

Antimicrobial agents and chemotherapy 20191022 11

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 transmiss ...[more]

PMID: 31481444

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Project description:The emergence of plasmid-mediated tigecycline resistance genes has attracted a great deal of attention globally. Currently, no comprehensive in-depth genomic epidemiology study of tet(X4)-bearing pathogens present of pork origin as the One Health approach has been performed. Herein, 139 fresh pork samples were collected from multiple regions in China and 58 tet(X4)-positive strains were identified. The tet(X4) gene mainly distributed in Escherichia coli (n = 55). Besides, 4 novel tet(X4)-positive bacterial species Klebsiella pneumoniae (n = 2), Klebsiella quasipneumoniae (n = 1), Citrobacter braakii (n = 1) and Citrobacter freundii (n = 1) were first characterized here. Four different core tet(X4)-bearing genetic environments and five types of tet(X4)-bearing tandem duplications were discovered among 58 strains. The results of the phylogenetic tree showed that there was some correlation between E. coli strains from pork, human, pig farms, and slaughterhouses. A total of seven types of plasmid replicons were found in tet(X4)-positive plasmids, among which multireplicon plasmids were observed. Notably, two tet(X4)-positive fusion plasmids pCSZ11R (IncX1-IncFIA-IncFIB-IncFIC) and pCSX5G-tetX4 (IncX1-IncFII-IncFIA) were formed by IS26 in the hot spot. Besides, six samples were identified to harbor two different tet(X4)-bearing strains. More interestingly, the absolute quantitative results showed that the expression levels of tet(X4) between different strains with different tet(X4) copies were approximate. In this study, the genetic environment of tet(X4)-positive plasmids containing different plasmid replicons was analyzed to provide a basis for the further development of effective control measures. It is also highlighted that animal-borne tet(X4)-bearing pathogens incur a transmission risk to consumed food. Therefore, there is an urgent need for large-scale monitoring as well as the development of effective control measures. IMPORTANCE Tigecycline was considered the last-line drug against serious infections caused by multidrug-resistant Gram-negative bacteria. However, the plasmid-mediated tigecycline resistance gene tet(X) has been widely reported in different sources of Enterobacterales and Acinetobacter in China. China is one of the largest pig-producing nations in the world, and in-depth investigation of gene in pork is vital to figure out the fundamental dissemination of these genes and set up a reasonable control framework. In this study, we conducted an in-depth and systematic analysis of the diversity of tet(X4)-positive plasmids and the genetic environment of tet(X4) contained in pork samples from multiple regions of China, providing a basis for further development of effective control measures. It is also highlighted that animal-borne tet(X4)-bearing pathogens incur a transmission risk to consumed food. Therefore, there is an urgent need for large-scale monitoring as well as the development of effective control measures.

Project description:The emergence of the plasmid-mediated high levels of the tigecycline resistance gene has drawn worldwide attention and has posed a major threat to public health. In this study, we investigated the prevalence of the tet(X4)-positive Enterobacterales isolates collected from a pig slaughterhouse and farms. A total of 101 tigecycline resistance strains were isolated from 353 samples via a medium with tigecycline, of which 33 carried tet(X4) (9.35%, 33/353) and 2 carried tet(X6) (0.57%, 2/353). These strains belong to seven different species, with Escherichia coli being the main host bacteria. Importantly, this report is the first one to demonstrate that tet(X4) was observed in Morganella morganii. Whole-genome sequencing results revealed that tet(X4)-positive bacteria can coexist with other resistance genes, such as blaNDM-1 and cfr. Additionally, we were the first to report that tet(X4) and blaNDM-1 coexist in a Klebsiella quasipneumoniae strain. The phylogenetic tree of 533 tet(X4)-positive E. coli strains was constructed using 509 strains from the NCBI genome assembly database and 24 strains from this study, which arose from 8 sources and belonged to 135 sequence types (STs) worldwide. We used Nanopore sequencing to interpret the selected 21 nonclonal and representative strains and observed that 19 tet(X4)-harboring plasmids were classified into 8 replicon types, and 2 tet(X6) genes were located on integrating conjugative elements. A total of 68.42% of plasmids carrying tet(X4) were transferred successfully with a conjugation frequency of 10-2 to 10-7. These findings highlight that diverse plasmids drive the widespread dissemination of the tigecycline resistance gene tet(X4) in Enterobacterales of porcine origin. IMPORTANCE Tigecycline is considered to be the last resort of defense against diseases caused by broad-spectrum resistant Gram-negative bacteria. In this study, we systematically analyzed the prevalence and genetic environments of the resistance gene tet(X4) in a pig slaughterhouse and farms and the evolutionary relationship of 533 tet(X4)-positive Escherichia coli strains, including 509 tet(X4)-positive E. coli strains selected from the 27,802 assembled genomes of E. coli from the NCBI between 2002 and 2022. The drug resistance of tigecycline is widely prevalent in pig farms where tetracycline is used as a veterinary drug. This prevalence suggests that pigs are a large reservoir of tet(X4) and that tet(X4) can spread horizontally through the food chain via mobile genetic elements. Furthermore, tetracycline resistance may drive tigecycline resistance through some mechanisms. Therefore, it is important to monitor tigecycline resistance, develop effective control measures, and focus on tetracycline use in the pig farms.

Dataset Information

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

Publications

Complete Nucleotide Sequence of a Novel Plasmid Bearing the High-Level Tigecycline Resistance Gene <i>tet</i>(X4).

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