Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1170540 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30970561.fastq.gz | Fastqsanger.gz | |||
| SRR30970562.fastq.gz | Fastqsanger.gz | |||
| SRR30970563.fastq.gz | Fastqsanger.gz | |||
| SRR30970564.fastq.gz | Fastqsanger.gz | |||
| SRR30970565.fastq.gz | Fastqsanger.gz |
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Project description:Background: The rapid evolution and dissemination of mobilized colistin resistance gene (mcr) family has revealed as a severe threat to the global public health. Nevertheless, dramatic reduction in the prevalence of mcr-1, the major member of mcr family, was observed after the withdrawal of colistin in animal fodder in China since 2017, demonstrating that colistin acts as a selective stress to promote the dissemination of mcr-1. As the second largest lineage, mcr-3 was firstly discovered in 2017 and has been identified from numerous sources. However, whether the spreading of mcr-3 is driven by colistin remains unknown. Methods: To this end, we investigated the global prevalence of mcr-3 from 2005 to 2022 by an up-to-date systematic review, along with a nation-wide epidemiological study to establish the change of mcr-3 prevalence in China before and after 2017. To investigate the fitness cost imposed by MCR-3 upon bacterial host, in vitro and in vivo competitive assays were employed, along with morphological study and fluorescent observation. Moreover, by replacing non-optimal codons with optimal codons, synonymous mutations were introduced into the 5’-coding region of mcr-3 to study mechanisms accounting for the distinct fitness cost conferred by MCR-1 and MCR-3. Furthermore, by combining AlphaFold and molecular dynamics (MD) simulation, we provided a complete characterization on the putative lipid A binding pocket localized at the linker domain of MCR-3. Crucially, inhibitors targeting at the putative binding pocket of MCR-1 or MCR-3 were identified from small molecules library using the pipeline of virtual screening. Findings: The global prevalence of mcr-3 increased continuously from 2005 to 2022. The average prevalence was 0.18% during 2005-2014 and rapidly increased to 3.41% during 2020-2022. The prevalence of mcr-3 in China increased from 0.79% in 2016 to 5.87% in 2019. We found that the fitness of mcr-3-bearing E. coli and empty plasmid control was comparable but higher than that of mcr-1-positive strain. Although the putative lipid A binding pocket of MCR-3 was similar to that of in MCR-1, mcr-3 occupies remarkable codon bias at the 5’-end of coding region that disrupted the stability of mRNA, further reduced its protein expression in E. coli, resulting in the low fitness burden of bacterial host. Moreover, the 5’-end codon usage frequency appeared as a critical factor related with the evolution of mcr family. Furthermore, based on the similar lipid A binding pocket among MCR family protein, we identified three novel MCR inhibitors targeting at such pocket by screening from small-molecule library, which effectively restored the colistin susceptibility of mcr-bearing E. coli. Interpretation: For the first time, we found that the prevalence of mcr-3 increased continuously during 2016-2019 in China, demonstrating that the withdrawal of colistin in husbandry failed to prevent the dissemination of mcr-3. Our study evidenced that the 5’-end codon bias appeared as a crucial regulator upon the fitness cost conferred by horizontally transferred genes. Most importantly, the putative lipid A binding pocket verified from current study was a promising target site for designing inhibitors against mcr-positive strains.
2025-06-29 | GSE300593 | GEO
Project description:mcr-1-carrying Escherichia coli isolates from Pigeons in China
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Project description:In this study, a whole-genome CombiMatrix Custom oligonucleotide tiling microarray with 90000 probes covering six sequenced Helicobacter pylori(H. pylori) genomes was designed and utilized for comparative genomic profiling of eight unsequenced strains isolated from patients with different gastroduodenal diseases in Heilongjiang province of China. Since significant genomic variation were found among these strains, an additional 76 H. pylori stains with different clinical outcomes isolated from various provinces of China were further tested by PCR to demonstrate this distinction. We observed several highly variable regions among strains of gastritis, gastric ulceration and gastric cancer. They are involved in genes associated with bacterial type I, type II and type III R-M system as well as in a virB gene neighboring the well studied cag pathogenic island. Previous studies have reported the diverse genetic characterization of this pathogenic island, but it is conserved in the strains tested by microarray in this study. Moreover, a number of genes involved in the type IV secretion system related to DNA horizontal transfer between H. pylori strains were identified based on the comparative analysis of the strain specific genes. These findings may provide new insights for discovering biomarkers for prediction of gastric diseases. Here we describe the design and use of a high-density oligonucleotide microarray covering six sequenced H. pylori genomes as well as several sequenced plasmids. The performance of this microarray is evaluated, and its utility is illustrated for the hybridization of genomic DNA in order to compare eight uncharacterized H. pylori strains which have not been sequenced with the six known, sequenced strains. We utilize this microarray to identify variable genomic region among H. pylori strains isolated from patients with different gastroduodenal diseases in a Chinese patient population. H. pylori isolates from 2 patients with chronic superficial gastritis, 2 patients with atrophic gastritis, 2 patients with gastric ulcer, and 2 patients with gastric cancer were studied. All eight strains were isolated from Heilongjiang province of China. A number of variable regions with high genetic diversity was identified. 26 selected genes were validated by large scale PCR in both microarray tested strains while an additional 76 strains were isolated from eight provinces.
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Project description:Neisseria meningitidis is a major cause of bacterial meningitis and septicemia worldwide. Seven new serogroup C meningococci were isolated from two provinces of China in January, 2006. Their PorA VR types were P1.20, 9. Multilocus sequence typing results indicated that they all belonged to ST-7. It is a new serogroup C N. meningitidis sequence type clone identified in China. Here we also present the results of a genomic comparison of these isolates with other 15 N. meningitidis serogroup A and B isolates, which belonged to ST-7, based on comparative genomic hybridization analysis. The data described here would be helpful to monitor the spread of this new serogroup C meningococci sequence type clone in China and worldwide. Keywords: comparative genomic hybridization
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Project description:Metagenomics of granular activated carbon from 7 cities across four provinces in China
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Project description:Gastric cancer is one of the most common malignant tumors. Asia has a high incidence of gastric cancer globally. South Korea, Mongolia, Japan and China are the four countries with the highest incidence of gastric cancer in the world. Gansu province in China has the estimated age-standardized incidence rates and mortality rates by Chinese standard population of 62.34/100,000 and 36.94/100,000, respectively, in 2012, which are much higher than the average level of China (22.06/100,000 and 15.16/100,000) in the same year. As a high incidence area of gastric cancer in China, Wuwei city in Gansu province has the prevalence of gastric cancer almost 5 times higher than the average level nationwide. In this study, the cancer tissues and matched adjacent normal mucosa tissues of 5 patients with early gastric cancers who were treated with ESD in Gansu Wuwei Tumor Hospital and the First Hospital of Lanzhou University were collected. All of the patients are from Gansu, China. MicroRNA array was used to find the differences in microRNAs expression profile between the early gastric cancer tissues and the para-cancer normal tissues. It is expected to explore the reasons of the abnormal high incidence of gastric cancer in Gansu Province, China, from the aspect of microRNAs expression profile characteristics.
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Project description:Persistent symptoms after COVID-19 infection can affect almost half of COVID-19 survivors, leading to poor quality of life. Despite its prevalence, the pathophysiology of this phenomenon is poorly understood. We analyzed differences in gene expression between patients with and without post-COVID symptoms in hospital, at follow-up, and longitudinally. As part of the Banque Québécoise de la COVID-19 biobank, 24 adult patients who were hospitalized due to respiratory COVID-19 were enrolled. Whole blood was collected within the first 10 days in hospital and 4-12 weeks after discharge. K-medoids clustering was performed to further separate patients into clusters/endotypes for DE analysis and pathway enrichment. We found that high rates of post-COVID symptoms in hospitalized patients were associated with an inability to mount, and subsequently resolve by 4-12 weeks after discharge, a robust early response involving immune and hemostatic pathways, which was seen in two of three endotypes.
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