Ontology highlight
ABSTRACT:
PROVIDER: PRJEB34874 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR3606450_1.fastq.gz | Fastqsanger.gz | |||
| ERR3606450_2.fastq.gz | Fastqsanger.gz | |||
| ERR3606460_1.fastq.gz | Fastqsanger.gz | |||
| ERR3606460_2.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:Acinetobacter baumannii is often highly resistant to multiple antimicrobials, posing a risk of treatment failure, and colistin is a "last resort" for treatment of the bacterial infection. However, colistin resistance is easily developed when the bacteria are exposed to the drug, and a comprehensive analysis of colistin-mediated changes in colistin-susceptible and -resistant A. baumannii is needed. In this study, using an isogenic pair of colistin-susceptible and -resistant A. baumannii isolates, alterations in morphologic and transcriptomic characteristics associated with colistin resistance were revealed. Whole-genome sequencing showed that the resistant isolate harbored a PmrBL208F mutation conferring colistin resistance, and all other single-nucleotide alterations were located in intergenic regions. Using scanning electron microscopy, it was determined that the colistin-resistant mutant had a shorter cell length than the parental isolate, and filamented cells were found when both isolates were exposed to the inhibitory concentration of colistin. When the isolates were treated with inhibitory concentrations of colistin, more than 80% of the genes were upregulated, including genes associated with antioxidative stress response pathways. The results elucidate the morphological difference between the colistin-susceptible and -resistant isolates and different colistin-mediated responses in A. baumannii isolates depending on their susceptibility to this drug.
2025-05-02 | GSE267612 | GEO
Project description:This study aims to determine the epidemiology of Enterobacteriaceae resistant to antibiotics of last resort in pregnant women in labour at a tertiary hospital, Pretoria, South Africa. Rectal swabs shall be used to screen for colonisation with CRE and colistin-resistant Enterobacteriales in pregnant women during labour. Carbapenem and colistin-resistant Enterobacterales can cause the following infections: bacteraemia; nosocomial pneumonia; urinary tract infections, and intra-abdominal infections. Due to limited treatment options, infections caused by these multidrug-resistant organisms are associated with a mortality rate of 40-50%. Screening for colonisation of carbapenem-resistant Enterobacteriaceae (CRE) and colistin-resistant Enterobacteriaceae will help implement infection and prevention measures to limit the spread of these multidrug-resistant organisms.
2022-07-20 | GSE208573 | GEO
Project description:Conjugative plasmids, major vehicles for the spread of antibiotic resistance genes, often contain multiple toxin‒antitoxin (TA) systems. However, the physiological functions of TA systems remain obscure. By studying TA families commonly found on colistin-resistant IncI2 mcr-1-bearing plasmids, we discovered that the HicAB TA, acts as a crucial addiction module to increase horizontal plasmid‒plasmid competition.
2024-12-25 | GSE284789 | GEO
Project description:Whole genome sequencing of mcr-1-positive Enterobacteriaceae
| PRJDB7066 | ENA
Project description:Identification of mobile colistin resistance genes (mcr-1.1, mcr-5, mcr-8.1) in Enterobacteriaceae of human and animal origins, Nigeria.
| PRJNA631965 | ENA