Polymorphism Existence of Mobile Tigecycline Resistance Gene tet(X4) in Escherichia coli.
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ABSTRACT:
SUBMITTER: Song H
PROVIDER: S-EPMC6985726 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Polymorphism Existence of Mobile Tigecycline Resistance Gene <i>tet</i>(X4) in Escherichia coli.
Song Huangwei H Liu Dejun D Li Ruichao R Fu Yulin Y Zhai Weishuai W Liu Xiao X He Tao T Wu Congming C Bai Li L Wang Yang Y
Antimicrobial agents and chemotherapy 20200127 2
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Project description:The recently emerged plasmid-mediated tigecycline resistance gene tet(X4) has mainly been detected in Escherichia coli but never in Klebsiella pneumoniae. Herein, we identified a clinical K. pneumoniae isolate that harbored the tet(X4) gene located on a non-self-transferable IncFII-type plasmid, which could be cotransferred with a conjugative plasmid to E. coli C600. The extending of bacterial species carrying tet(X4) suggested the increasing risk of spreading mobile tigecycline resistance genes among important pathogens in clinical settings. IMPORTANCE Tigecycline, the first member of glycylcycline class antibiotic, is often considered one of the effective antibiotics against multidrug-resistant (MDR) infections. However, the emergence and wide distribution of two novel plasmid-mediated tigecycline resistance genes, tet(X3) and tet(X4), pose a great threat to the clinical use of tigecycline. The newly tet(X) variants have been identified from multiple different bacterial species, but the tet(X) variant in the Klebsiella pneumoniae strain has been reported only once before. In this study, we identified a clinical K. pneumoniae isolate that harbored a non-self-transferable tet(X4)-carrying plasmid. This plasmid has never been found in other tet(X4)-harboring strains and could be cotransferred with a conjugative plasmid to the recipient strain. Our findings indicate that the tet(X4) gene breaks through its original bacterial species and spreads to some important nosocomial pathogens, which posed a serious threat to public health.
| S-EPMC8826827 | biostudies-literature
Project description:Emergence of pathogens harboring tigecycline resistance genes incurs great concerns. Wastewater is recognized as the important reservoir of antimicrobial resistance genes. Here we characterized the phenotypes and genotypes of bacteria carrying tet(X4) from wastewater in Turkey for the first time. Four tet(X4)-positive Escherichia coli isolates were identified and characterized by PCR, Sanger sequencing, antimicrobial susceptibility testing, conjugation assays, Illumina sequencing, nanopore sequencing and bioinformatic analysis. Four tet(X4)-harboring isolates were multidrug-resistant (MDR) bacteria and the tet(X4) gene was nontransferable in four isolates. Genetic analysis revealed that tet(X4) genes in four isolates were located on plasmids co-harboring two replicons IncFIA(HI1) and IncFIB(K). However, none of the four plasmids carried genes associated with horizontal transfer of plasmids. The coexistence of blaSHV-12-bearing IncX3-type plasmid and tet(X4)-harboring plasmid was also found in one isolate. These findings indicate that continuous surveillance of the tet(X4)-bearing isolates in different environments worldwide should be strengthened. IMPORTANCE The emergence of tigecycline resistance genes in humans and animals in China seriously threatens the clinical utility of tigecycline, but the molecular epidemiology of tigecycline-resistant bacteria in other countries remained largely unknown. Therefore, it is necessary to learn the prevalence and molecular characteristics of bacteria carrying tigecycline resistance genes, particularly the mobilizable tet(X4), in other countries. In the study, we first described the presence and molecular characteristics of the tet(X4)-positive E. coli isolates from wastewater in Turkey. Four tet(X4)-bearing isolates belonged to ST609, an E. coli clone commonly found from humans, animals and the environment. These findings highlight the importance of monitoring the tet(X4) gene in different settings globally.
| S-EPMC9431179 | biostudies-literature
Project description:The recent emergence of plasmid-mediated tigecycline resistance genes, tet(X3) and tet(X4), in animals and humans in China would pose a foreseeable threat to public health. To illustrate this paradigm shift in tigecycline resistance, here, covering the period 2008-2018, we retrospectively analysed a national strain collection of Escherichia coli (n = 2254), obtained from chickens and pigs, in six representative provinces of China. The gene tet(X4) was identified in five pig isolates collected in 2016 and 2018 from the provinces of Sichuan (3/15, 2018), Henan (1/25, 2018) and Guangdong (1/28, 2016), but not in the isolates prior to 2016. None of the isolates was detected harbouring tet(X3). All tet(X4)-positive E. coli exhibited high levels of tigecycline resistance (MICs, 16-64 mg/L), and two were confirmed as colistin resistant, harbouring chromosome-borne mcr-1 gene. The gene tet(X4) was detected on a plasmid in all five isolates, whereas a co-location of tet(X4) on the chromosome of one isolate was observed. Diverse host strains and novel plasmids related to the tet(X4) gene were observed. Our timely findings of the recent emergence of tet(X4) gene in food animal support the rapid surveillance and eradication of this gene before it is established.
| S-EPMC6818123 | biostudies-literature
Project description:Public health interventions to control the recent emergence of plasmid-mediated tigecycline resistance genes rely on a comprehensive understanding of its epidemiology and distribution over a wide range of geographical scales. Here we analysed an Escherichia coli collection isolated from pigs and chickens in China in 2018, and ascertained that the tet(X4) gene was not present at high prevalence across China, but was highly endemic in northwestern China. Genomic analysis of tet(X4)-positive E. coli demonstrated a recent and regional dissemination of tet(X4) among various clonal backgrounds and plasmids in northwestern China, whereas a parallel epidemic coincided with the independent acquisition of tet(X4) in E. coli from the remaining provinces. The high genetic similarity of tet(X4)-positive E. coli and human commensal E. coli suggests the possibility of its spreading into humans. Our study provides a systematic analysis of the current epidemiology of tet(X4) and identifies priorities for optimising timely intervention strategies.
| S-EPMC7395754 | biostudies-literature
Project description: Not available
| S-EPMC8627205 | biostudies-literature
Project description:This study aimed to investigate the prevalence and characterization of tet(X4) in Escherichia coli isolates from a pig farm in Shanghai, China, and to elucidate tet(X4) dissemination mechanism in this swine farm. Forty-nine (80.33%) E. coli strains were isolated from 61 samples from a pig farm and were screened for the presence of tet(X). Among them, six (12.24%) strains were positive for tet(X4) and exhibited resistance to tigecycline (MIC ≥ 16 mg/L). They were further sequenced by Illumina Hiseq. Six tet(X4)-positive strains belonged to ST761 with identical resistance genes, resistance profiles, plasmid replicons, and cgMLST type except that additional ColE10 plasmid was present in isolate SH21PTE35. Isolate SH21PTE31, as a representative ST761 E. coli strain, was further sequenced using Nanopore MinION. The tet(X4) in SH21PTE31 was located on IncFIA18/IncFIB(K)/IncX1 hybrid plasmid pYUSHP31-1, highly similar to other tet(X4)-carrying IncFIA18/IncFIB(K)/IncX1 plasmids from ST761 E. coli and other E. coli lineages in China. These IncFIA18/IncFIB(K)/IncX1 plasmids shared closely related multidrug resistance regions, and could reorganize, acquire or lose resistance modules mediated by mobile elements such as ISCR2 and IS26. Phylogenetic analysis were performed including all tet(X4)-positive isolates obtained in this pig farm combined with 43 tet(X4)-positive E. coli from pigs, cow, pork, wastewater, and patients with the same ST from NCBI. The 50 tet(X4)-carrying E. coli ST761 isolates from different areas in China shared a close phylogenetic relationship (0-49 SNPs). In conclusion, clonal transmission of tet(X4)-positive E. coli ST761 has occurred in this swine farm. E. coli ST761 has the potential to become a high-risk clone for tet(X4) dissemination in China.
| S-EPMC9396132 | biostudies-literature
Project description: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.
| S-EPMC6811429 | biostudies-literature
Project description:The emergence and widespread of tigecycline resistance undoubtedly poses a serious threat to public health globally. The exploration of combination therapies has become preferred antibacterial strategies to alleviate this global burden. In this study, tigecycline-resistant tet(X4)-positive Escherichia coli were selected for adjuvant screening. Interestingly, 9-aminominocycline (9-AMC), one of the tigecycline metabolites, exhibits synergistic antibacterial activity with tigecycline using checkerboard assay. The efficacy in vitro and in vivo was evaluated, and the synergistic mechanism was further explored. The results suggested that 9-AMC combined with tigecycline could inhibit the growth of antibiotic resistant bacteria, efficiently retard the evolution of tet(X4) gene and narrow the drug mutant selection window. In addition, the combination of tigecycline and 9-AMC could destroy the normal membrane structure of bacteria, inhibit the formation of biofilm, remarkably reduce the level of intracellular ATP level, and accelerate the oxidative damage of bacteria. Furthermore, 9-AMC is more stable in the bind of Tet(X4) inactivating enzyme. The transcriptomics analysis revealed that the genes related to the 9-AMC and tigecycline were mainly enriched in ABC transporters. Collectively, the results reveal the potentiation effects on tigecycline and the probability of 9-AMC as a novel tigecycline adjuvant against tet(X4)-positive Escherichia coli, which provides new insights for adjuvant screening.
| S-EPMC11264248 | biostudies-literature
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.
| S-EPMC8694195 | biostudies-literature
Project description:Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria1. Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection2,3. Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics.
| S-EPMC6707864 | biostudies-literature