Escherichia coli K1 colibactin
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR863168_1.fastq.gz | Fastqsanger.gz | |||
| ERR863168_2.fastq.gz | Fastqsanger.gz |
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Project description:Colibactin, a potent genotoxin of Escherichia coli, causes DNA double strand breaks (DSBs). We investigated if colibactin creates a particular DNA damage signature in infected human cells. Genomic contexts of colibactin-induced DSBs were enriched for a distinct AT-rich hexameric sequence motif. A survey of somatic mutations at the colibactin target sites of several thousand cancer genomes revealed significant enrichment of the motif in colorectal cancers. Moreover, the exact break point location corresponded with mutational hot spots in these cancers corresponding to a distinct trinucleotide signature. This work provides evidence for a role of colibactin in the etiology of human cancer.
2020-04-22 | GSE145594 | GEO
Project description:Various bacteria are suggested to contribute to colorectal cancer (CRC) development, including pks+ E. coli, which produces the genotoxin colibactin that induces characteristic mutational signatures in host epithelial cells. However, it remains unclear how the highly unstable colibactin molecule is able to access host epithelial cells to cause harm. Using the microbiota-dependent ZEB2-transgenic mouse model of invasive CRC, we demonstrate that the oncogenic potential of pks+ E. coli critically depends on bacterial adhesion to host epithelial cells, mediated by the type-1 pilus adhesin FimH and the F9-pilus adhesin FmlH. Blocking bacterial adhesion using a pharmacological FimH inhibitor attenuates colibactin-mediated genotoxicity and CRC exacerbation. We also show that allelic switching of FimH strongly influences genotoxic potential of pks+ E. coli and can induce a genotoxic gain-of-function in the probiotic strain Nissle 1917. Adhesin-mediated epithelial binding subsequently allows the production of the genotoxin colibactin in close proximity to host epithelial cells, which promotes DNA damage and drives CRC development. These findings present promising therapeutic avenues for the development of anti-adhesive therapies aimed at mitigating colibactin-induced DNA damage and inhibiting the initiation and progression of CRC, particularly in individuals at risk for developing CRC.
2024-08-19 | GSE241851 | GEO
Project description:By comparing the transcriptome profile upon deletion or overexpression of ClbR or ClbQ, we addressed the role of these proteins in regulation of colibactin expression. Our global screen indicates that ClbR is the key transcriptional activator of colibactin expression. In addition, we further investigated potential transcription start sites of the colibactin determinant.
2020-01-17 | GSE143807 | GEO
Project description:The complex reservoir of metabolite-producing bacteria in the gastrointestinal tract contributes tremendously to human health and disease. Bacterial composition, and by extension gut metabolomic composition, is undoubtably influenced by the use of modern antibiotics. Herein, we demonstrate that polymyxin B, a last resort antibiotic used for chronic multidrug resistant infections infections, influences the production of the genotoxic metabolite colibactin from adherent-invasive Escherichia coli (AIEC) NC101. Colibactin can augment colorectal cancer (CRC) through DNA double stranded breaks and interstrand crosslinks. While the structure and biosynthesis of colibactin has been elucidated, chemical-induced regulation of its biosynthetic gene cluster and subsequent production of the genotoxin by pathogenic E. coli are largely unexplored. This research highlights the regulation of the colibactin-producing biosynthetic gene cluster under polymyxin stress. Using a multi-omic approach, we have identified that polymyxin stress enhances the abundance of colibactin biosynthesis proteins (Clb’s) in multiple pks+ E. coli strains, including pro-carcinogenic AIEC: NC101, the probiotic strain: E. coli Nissle 1917, and the antibiotic testing strain: E. coli ATCC 25922. Expression analysis via qPCR revealed that increased transcription of clb genes likely contributes to elevated Clb protein levels in NC101. Enhanced production of Clb’s by NC101 under polymyxin stress matched an increased production of the colibactin prodrug motif, a proxy for the mature genotoxic metabolite. Furthermore, E. coli with heightened tolerance for polymyxin antibiotics induced greater DNA damage, assessed by quantification of γH2AX staining in cultured intestinal epithelial cells. This study establishes a key link between the polymyxin B stress response and colibactin production in pks+ E. coli. Ultimately, our findings will inform future studies investigating colibactin regulation, the microbial response to antibiotics in the gut, and the ability of seemingly innocuous commensal microbes to induce host disease.
2021-07-15 | PXD025088 | Pride
Project description:Pathoadaptative mutations of E. coli K1 in experimental neonatal infection
| PRJEB14305 | ENA
Project description:Preterm birth is currently the leading cause of neonatal morbidity and mortality. Genetic, immunological and infectious causes are suspected. Preterm infants have a higher risk of severe bacterial neonatal infections, most of which are caused by Escherichia coli an in particular E. coli K1strains. Women with history of preterm delivery have a high risk of recurrence and therefore constitute a target population for the development of vaccine against E. coli neonatal infections. Here, we characterized the immunological, microbiological and protective properties of a live attenuated vaccine candidate in adult female mice and their pups against after a challenge by K1 and non-K1 strains of E. coli. Our results show that the E. coli K1 E11 aroA vaccine induces strong immunity, driven by polyclonal bactericidal antibodies. In our model of meningitis, pups born to mothers immunized before mating were well protected against various K1 and non-K1 strains of E. coli. Given the very high mortality rate and the neurological sequalae associated with neonatal E. coli K1 meningitis, our results constitute preclinical proof of concept for the development of a live attenuated vaccine against severe E. coli infections in women at risk of preterm delivery.
2024-01-02 | GSE252194 | GEO
Project description:Bioluminescent Imaging Reveals Novel Patterns of Colonization and Invasion in Systemic Escherichia coli K1 Experimental Infection in the Neonatal Rat
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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of transfected NC K1 cells and transfected si-NEAT1_2 K1 cells. The goals of this study are to analysis the different mRNA expression between transfected NC K1 cells and transfected si-NEAT1_2 K1 cells. Quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis. We performed mRNA-seq in the NEAT1_2 knockdown group and NC group in the K1 cell line. We found that after knockdown of NEAT1_2, 615 mRNAs were upregulated and 2364 mRNAs were downregulated.
2020-12-05 | GSE159905 | GEO
Project description:Bacillus sp. K1 strain:k1 | isolate:k1 Genome sequencing
| PRJNA816635 | ENA