Bile_Salt_Hydrolase_engineered strains
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Na
SUBMITTER: 
Pieter C Dorrestein
PROVIDER: MSV000094578 | MassIVE | Sat Apr 20 23:15:00 BST 2024
REPOSITORIES: MassIVE
Similar Datasets
Project description:We designed probes to understand bile salt hydrolase substrate specificity in the mousegut microbiome.
2024-06-04 | PXD052119 | Pride
Project description:Listeria monocytogenes is a gram-positive, facultative anaerobe food-borne pathogen that is the causative agent of listeriosis. Upon ingestion, L. monocytogenes is subjected to a variety of non-specific host defenses such as bile. The main component of bile is bile salts which is known to be bactericidal through inducing DNA damage, oxidative damage, membrane instability, and protein misfolding. Previous studies have focused mainly on aerobic conditions; however the human GI tract is an environment ranging from microaerophilic to anaerobic. The bile salt hydrolase, an enzyme known to reduce toxicity of bile through hydrolysis, has been shown to have an increase in activity under anaerobic conditions. Therefore, the purpose of this study was to determine the effect of oxygen on bile resistance and determine the bile specific proteome that is responsible for this. To do this, we performed survival assays on virulent strains: F2365, 10403S, EGDe and avirulent strain, HCC23. Results showed an increase in viability for all virulent strains when exposed to porcine bile under anaerobic conditions. Interestingly, an increase in resistance was seen in HCC23 only under aerobic conditions. We then used a total proteomic analysis approach to compare the bile specific proteome under both aerobic and anaerobic conditions. Results showed many difference between all strains including an increase in abundance of proteins associated with stress responses, repair, cell morphology, and cell division under anaerobic conditions. Response to bile salt stress showed to be strain dependent. This study not only identified proteins responsible for L. monocytogenes bile resistance but also differerences between aerobic and anaerobic conditions thus suggesting that oxygen availability is not only a stressor but in some way providing assistance to overcoming bile salts.
2017-05-03 | PXD002243 | Pride
Project description:E. coli DH5a expressing bile salt hydrolase variants in the presence of 1 mM glycocholate (GCA), taurocholate (TCA), or cholate (CA).
2023-06-09 | MSV000092138 | MassIVE
Project description:The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-b-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.
2018-07-19 | GSE112571 | GEO
Project description:Escherichia coli transformed with bile salt hydrolase gene from Bifidobacterium is treated with conjugated (TCA/GCA) and unconjugated (CA/DCA) bile acids and grown overnight.
2022-07-07 | MSV000089837 | GNPS
Project description:A selective gut bacterial bile salt hydrolase alters host metabolism
| PRJNA448196 | ENA
Project description:Bifidobacterium longum is treated with/without GR-7 (Bile salt hydrolase inhibitor) and Cholic acid/Deoxycholic acid and grown for 8 hrs.
2022-07-07 | MSV000089835 | GNPS
Project description:Listeria monocytogenes is a gram-positive, food-borne pathogen responsible for invasive infections with high overall mortality. Early host defenses encountered by L. monocytogenes following ingestion include low pH of the stomach and bile present in the small intestinal lumen. We hypothesized that “epidemic” strains are better able to withstand exposure to low pH and bile encountered in the gastrointestinal tract as compared to most “environmental” strains. Furthermore, we hypothesized that epidemic and environmental strains would have distinct transcriptional programs upon exposure to these conditions. Our treatments included 1 hr exposure to acid (pH 5.5 and 3.5) and bile (0.3%) stress. Strains were pre-exposed to pH 5.5 (1 hr) before being treated with pH 3.5. We used a collection of 12 previously characterized epidemic and environmental strains and each strainXtreatment combination included 3 biological replicates for each microarray experiment. All microarray experiments were two color competitive hybridizations that paired experimental conditions with the same strain at neutral pH for acid stress and pH 5.5 for bile stress. Transcriptomes of environmental strains exposed to acid and bile stress showed remarkably greater number of genes with differences of ≥2-fold expression levels as compared to epidemic strains (5 and 7, respectively). Environmental strains were characterized by up-regulation of several stress related genes and down-regulation of several cell envelope biosynthesis and virulence related genes, suggesting that complex regulatory networks orchestrate the cellular changes in the environmental strains to overcome stressful environments. The transcriptome of epidemic strains, in contrast, showed muted responses to these stress conditions implying their pre-adaptability to acid and bile stress encountered during natural infection that may enable epidemic strains to survive and become “primed” for subsequent colonization and infection in the lower gastrointestinal tract. Keywords: stress response, comparative transcriptomics, acid-adaptation, differential virulence, acid-stress response, bile-stress response
2009-06-15 | GSE10603 | GEO
Project description:Bifidobacterium are considered to be beneficial for human health and are classified as probiotic bacterium. They must resist many environmental stress factors in order to survive in the gastrointestinal environment including; pH, oxygen availability, bile and nutrient starvation (eg: iron or carbon). This study investigates Bifidobacterium breve UCC2003 global genome response to growth under ferrous and/or ferric iron limiting conditions. Revealing that growth under iron limitation effects many processes in the cell including carbon and nitrogen metabolism and induces/reduces the expression of numerous genes; including multiple iron uptake systems, DPS proteins (which are predicted to be involved in iron storage/DNA protection), Fe-S cluster associated proteins and a bile salt hydrolase (bshB). Insertional mutagenesis and survival assays were employed and demonstrated that iron starvation imposed on B. breve UCC2003 results in an increased resistance to bile stress due to in part the iron-inducible transcription of the bshB gene. Furthermore, this study links BSH activity in B. breve UCC2003 to its ability to survive the deleterious effects of bile salt and suggest that B. breve UCC2003 may be use iron as a signal to adapt to the constantly changing environment within the small intestine.
2018-03-31 | GSE110080 | GEO
Project description:Microbial transformation of bile acids affects intestinal immune homeostasis but its impact on inflammatory pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that T cell-driven inflammation decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of unconjugated and microbe-derived bile acids. Several microbe-derived bile acids attenuated farnesoid X receptor (FXR) activation, suggesting that loss of these metabolites during inflammation may increase FXR activity and exacerbate the course of disease. Indeed, mortality increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells during mouse GVHD. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and microbe-derived bile acids. Additionally, the FXR antagonist ursodeoxycholic acid reduced the proliferation of human T cells and was associated with a lower risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of microbe-derived bile acids during inflammation may be an important mechanism to amplify T cell-mediated diseases.
2024-02-09 | GSE253360 | GEO