Escherichia coli LF82
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA487828 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:LF82, an adherent invasive Escherichia coli (AIEC) pathobiont, is associated with Crohn’s disease, an inflammatory bowel disease of unknown etiology. No genetic features have been identified that distinguish AIEC strains, such as LF82, from “commensal” or pathogenic E. coli. We investigated an extremely rare single nucleotide polymorphism (SNP) within the highly conserved rpoD gene, encoding sigma70 [primary sigma factor, RNA polymerase (RNAP)]. We demonstrate that sigma70 D445V results in transcriptome and phenotypic changes consistent with LF82 phenotypes, including increased biofilm formation and antibiotic resistance. The position of D445V within RNAP is predicted to affect spacer interaction; in vitro transcriptions reveal that the variant increases transcription from several promoters with a 16 bp spacer and a -14G:C. Our work demonstrates that a single SNP within the bacterial primary sigma can lead to myriad gene expression changes/ new phenotypes and suggests an underrecognized mechanism by which pathobionts and other strain variants can emerge.
2024-09-30 | GSE253924 | GEO
Project description:Adherent-Invasive Escherichia coli Transcriptome
| PRJNA752090 | ENA
Project description:Imbalance in beneficial and harmful bacteria underlies gastrointestinal diseases, such as inflammatory bowel disease. Here, we demonstrated that certain E. coli strains, specifically adherent-invasive E. coli (AIEC), utilize a serine metabolism pathway to outcompete other E. coli strains in the inflamed gut. In contrast, amino acid metabolism has a minimal effect on their competitive fitness in the healthy gut. The availability of luminal serine used for the competition of E. coli is largely dependent on dietary intake, as the inflammation-induced blooms of AIEC are significantly blunted when amino acids, particularly serine, are removed from the diet. Thus, intestinal inflammation regulates the intraspecific competition between Enterobacteriaceae by eliciting their metabolic reprogramming.
2019-09-06 | GSE106412 | GEO
Project description:Current clinical antibiotics are largely broad-spectrum agents that promote intestinal dysbiosis and colonisation of Enterobacteriaceae, which are often drug-resistant. Indeed, dysbiosis creates an ideal niche for adherent-invasive Escherichia coli (AIEC) in patients with inflammatory bowel disease (IBD). There is an urgent and unmet need for novel narrow-spectrum and microbiome-sparing antibiotics. Here, we screened >10,000 molecules for antibacterial activity against AIEC and discovered enterololin, an antibacterial compound with targeted activity against Enterobacteriaceae species. Molecular substructure- and deep learning-guided mechanism of action investigations revealed that enterololin perturbs lipoprotein trafficking through a mechanism involving the LolCDE complex. Moreover, enterololin can suppress an AIEC infection in mouse models, while largely preserving the overall microbiome composition. This work highlights the utility of deep learning methods for predicting molecular interactions, thereby accelerating mechanism of action elucidation of novel molecules, and identifies a promising Enterobacteriaceae-specific antibacterial candidate for further development to treat challenging infections in IBD patients.
2025-08-27 | GSE300731 | GEO
Project description:Our aim was to identify candidate transcripts that distinguish AIEC from non-invasive E. coli (NIEC) strains and might be useful for rapid and accurate identification of AIEC by culture-independent technology. We performed comparative RNA-Sequence (RNASeq) analysis using AIEC strain LF82 and NIEC strain HS during exponential and stationary growth.
2017-02-09 | GSE69020 | 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:Type IV secretion systems (T4SSs) are central to bacterial pathogenesis due to their versatile functions. While traditionally known for their role in DNA transfer via conjugation and secretion of effector proteins, T4SSs have been shown to mediate biofilm formation in various bacteria. These biofilms are critical for the fitness of adherent-invasive strains of Escherichia coli (AIEC), which are commonly isolated from Crohn’s disease patients and are known for propelling gut inflammation. Many AIEC strains carry F-like plasmids encoding the IncF subgroup of T4SSs. Unlike minimized systems that comprise 12 core components, the IncF family has evolved into an expanded T4SS through the acquisition of additional genes that enhance conjugation. Here, we show that a biofilm-forming AIEC strain harbors an unusual IncF plasmid that lacks two conserved components otherwise considered essential for T4SS functionality. We demonstrate that this strain forms a natural hybrid T4SS, where the two components missing in the plasmid are supplied by a co-residing chromosomal T4SS present on an integrative and conjugative element (ICE). Using biochemical assays, we show that this functional machine is a mosaic of IncF and ICE-encoded proteins that co-operatively drive pilin polymerization and biofilm formation on epithelial cells. Furthermore, we show that a subpopulation of bacteria expresses the IncF and ICE-encoded genes in response to host cells, leading to the assembly of biofilms that promote AIEC fitness in the gut. Together, these findings uncover a crosstalk between two co-residing and evolutionary distant mobile genetic elements to form a hybrid T4SS that mediates biofilm biogenesis by a Crohn’s disease-associated pathogen.
2025-07-23 | PXD066462 | Pride
Project description:The role of propionate-induced rearrangement of membrane proteins in the formation of the virulent phenotype of Crohn's Disease-associated adherent-invasive Escherichia coli. Adhesive-invasive Escherichia coli (AIEC) were first isolated from the ileal mucosa of a patient with Crohn's disease (CD) which is a severe chronic immune-mediated granulomatous inflammatory disease of the gastrointestinal tract. It turned out that they are able to successfully penetrate the mucin layer, overcome the epithelial barrier, and also survive and multiply inside macrophage. Bacteria with such properties were assigned to a special group of pathobiont adhesive-invasive E. coli. AIEC activity is accompanied by the release of pro-inflammatory cytokines, i.e. surviving and multiplying inside macrophages, they enhance the inflammatory process. The role of AIEC in the onset or chronicity of CD is not well-defined. However, it has been proposed that these bacteria could trigger the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to their survival within macrophages, they could stimulate chronic inflammation and granuloma developmen. Pathogens use a variety of mechanisms, including the induction of inflammation, the direct or indirect destruction of commensal species, and the use of alternative carbon sources to survive. AIEC are shown to be able to utilize ethanolamine and propanediol, which are formed during the catabolism of phospholipids, fucose or rhamnose, propionate and other metabolites. Metabolic plasticity is thought to allow AIEC to act as an opportunistic pathogen in conditions of intestinal inflammation. We have previously shown that passage of AIEC from a CD patient (CD isolate) on M9 minimal medium supplemented with sodium propionate (PA) as a carbon source leads to a strong increase, and passage on M9 medium supplemented with glucose, on the contrary, leads to a significant decrease in adhesive-invasive properties and ability to survive in macrophages. We were able to compare the isogenic CD isolate in two states: virulent with high adhesive-invasive activity and ability to survive in macrophages, and non-virulent, when these properties are lost. In contrast to the CD isolate, passage of the laboratory strain K12 Mg1655 on the M9 medium supplemented with PA did not cause a similar effect. We performed a comparative proteomic analysis of membrane fractions isolated from ZvL2-PA and ZvL2-GLU using LC-MS. The laboratory strain K12 Mg1655 was used as a control.
2025-05-07 | PXD054715 | Pride