Detection of the mobile tigecycline resistance gene tet(X4) in Escherichia coli from pigs in the United Kingdom
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ABSTRACT:
PROVIDER: PRJEB43587 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| Other | ||||
| ERR5456210_1.fastq.gz | Fastqsanger.gz | |||
| ERR5456210_2.fastq.gz | Fastqsanger.gz |
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Project description: Not available
| S-EPMC6985726 | biostudies-literature
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:Idiomarina sp. X4 strain:X4 Assembly
| PRJNA419615 | ENA
Project description:Pseudomonas sp. X4 strain:X4 Genome sequencing
| PRJNA1131293 | ENA
Project description:Tigecycline is a broad-spectrum active intravenous antibiotic that is also active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason for the increase is not yet clear. In this study, we found tigecycline could cause abnormal coagulation in tumor patients, especially in patients with hematological malignancies. The main manifestations were decreased fibrinogen and prolonged activated prothrombin time (APTT), thrombin time (TT) and D-dimer. In addition, functional studies have found that tigecycline could inhibit platelet adhesion and aggregation, and the patient's coagulation function could gradually recover after discontinuation. Gene sequencing results suggested that tigecycline could significantly regulate the expression of genes related to platelet function pathways, and could increase the incidence of single nucleotide polymorphisms and the number of alternative splices in CHO cells with tigecycline treatment. Abnormal platelet function and low numbers are common in patients with hematological malignancies. Our study could explain the mechanism of abnormal coagulation caused by tigecycline. At the same time, a warning should be given when doctors applied tigecycline to cure infections in tumor patients.
2022-06-01 | GSE198830 | GEO
Project description:Tigecycline, a protein translation inhibitor, is a treatment of last resort for infections caused by the opportunistic multidrug resistant human pathogen Acinetobacter baumannii. However, strains resistant to tigecycline were reported not long after its clinical introduction. Translation inhibitor antibiotics perturb ribosome function and induce the reduction of (p)ppGpp, an alarmone involved in the stringent response that negatively modulates ribosome production. Through RNA sequencing, this study revealed a significant reduction in the transcription of genes in citric acid cycle and cell respiration, suggesting tigecycline inhibits or slows down bacterial growth. Our results indicated that the drug-induced reduction of (p)ppGpp level promoted the production but diminished the degradation of ribosomes, which mitigates the translational inhibition effect by tigecycline. The reduction of (p)ppGpp also led to a decrease of transcription coupled nucleotide excision repair which likely increases the chances of development of tigecycline resistant mutants. Increased expression of genes linked to horizontal gene transfer were also observed. The most upregulated gene, rtcB, involving in RNA repair, is either a direct tigecycline stress response or is in response to the transcription de-repression of a toxin-antitoxin system. The most down-regulated genes encode two b-lactamases, which is a possible by-product of tigecycline-induced reduction in transcription of genes associated with peptidoglycan biogenesis. This transcriptomics study provides a global genetic view of why A. baumannii is able to rapidly develop tigecycline resistance.
2020-08-03 | GSE131451 | GEO
Project description:Phytobacter sp. X4 strain:X4 Genome sequencing and assembly
| PRJNA853855 | ENA
Project description:Genomic epidemiology of Candida auris within the United Kingdom
| PRJEB26393 | ENA
Project description:We isolated 47 Acinetobacter strains carrying tet(X3) and 4 ST767 E. coli strains carrying tet(X4) from 296 rectal swab samples from dairy cows on a Chinese farm. tet(X3) was located on chromosomes or diverse plasmids, and tet(X4) was located on IncFIBκ/FIA(HI1)/X1 nontransferable plasmid. The coexistence of tet(X3) and carbapenemase genes, including blaOXA-58 and blaNDM-1, was detected in 9 Acinetobacter spp. These findings suggested that the use of tetracycline and other antibiotics in food production warrants urgent attention.
| S-EPMC7577139 | biostudies-literature
Project description:BackgroundTigecycline is a tetracycline derivative that constitutes one of the last-resort antibiotics used clinically to treat infections caused by both multiple drug-resistant (MDR) Gram-negative and Gram-positive bacteria. Resistance to this drug is often caused by chromosome-encoding mechanisms including over-expression of efflux pumps and ribosome protection. However, a number of variants of the flavin adenine dinucleotide (FAD)-dependent monooxygenase TetX, such as Tet(X4), emerged in recent years as conferring resistance to tigecycline in strains of Enterobacteriaceae, Acinetobacter sp., Pseudomonas sp., and Empedobacter sp. To date, mechanistic details underlying the improvement of catalytic activities of new TetX enzymes are not available.ResultsIn this study, we found that Tet(X4) exhibited higher affinity and catalytic efficiency toward tigecycline when compared to Tet(X2), resulting in the expression of phenotypic tigecycline resistance in E. coli strains bearing the tet(X4) gene. Comparison between the structures of Tet(X4) and Tet(X4)-tigecycline complex and those of Tet(X2) showed that they shared an identical FAD-binding site and that the FAD and tigecycline adopted similar conformation in the catalytic pocket. Although the amino acid changes in Tet(X4) are not pivotal residues for FAD binding and substrate recognition, such substitutions caused the refolding of several alpha helixes and beta sheets in the secondary structure of the substrate-binding domain of Tet(X4), resulting in the formation of a larger number of loops in the structure. These changes in turn render the substrate-binding domain of Tet(X4) more flexible and efficient in capturing substrate molecules, thereby improving catalytic efficiency.ConclusionsOur works provide a better understanding of the molecular recognition of tigecycline by the TetX enzymes; these findings can help guide the rational design of the next-generation tetracycline antibiotics that can resist inactivation of the TetX variants.
| S-EPMC8666040 | biostudies-literature