Eggerthella lenta DSM 2243
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA21093 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR017650.fastq.gz | Fastqsanger.gz | |||
| SRR017651.fastq.gz | Fastqsanger.gz | |||
| SRR017652.fastq.gz | Fastqsanger.gz | |||
| GCA_000024265.1_sequence_report.txt | Txt |
Items per page: 5 1 - 4 of 4 |
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Project description:Bile acids are not only crucial for the uptake of lipids, but also have widespread systematic ef-fects and shape the gut-microbiome composition. Bile acids can directly shape the gut-microbiome and can be modified by bacteria such as Eggerthella lenta which in turn plays a crucial role in host metabolism and immune response. We cultivated eight strains that represent a simplified human intestinal microbiome and inves-tigated the molecular response to bile acids, co-culturing with Eggerthella lenta and the combina-tion. We observed growth inhibition of particularly gram-positive strains during bile acid stress, which could be alleviated through co-culturing with Eggerthella lenta. The inhibition of growth was related to a decrease in membrane integrity and genotoxic effects of bile acids, which we investigated using zeta potential measurements in combination with proteomic and metabolomic analyses. Co-culturing with Eggerthella lenta alleviated stress through formation of oxidized and epimer-ized bile acids and the molecular response to co-culturing was seen to be strain specific. We also note that we could detect the recently described Microbial Bile Salt Conjugates in our cultures. This study highlights the significance of a potent bile acid modifier and how in-depth molecular analyses are required to decipher cross-communication between gut and host.
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Project description:Strains of Eggerthella lenta are capable of oxidation-reduction reactions capable of oxidizing and epimerizing bile acid hydroxyl groups. Several genes encoding these enzymes, known as hydroxysteroid dehydrogenases (HSDH) have yet to be identified. It is also uncertain whether the products of E. lenta bile acid metabolism are further metabolized by other members of the gut microbiota. We characterized a novel human fecal isolate identified as E. lenta strain C592. The complete genome of E. lenta strain C592 was sequenced and comparative genomics with the type strain (DSM 2243) revealed high conservation, but some notable differences. E. lenta strain C592 falls into group III, possessing 3?, 3?, 7?, and 12?-hydroxysteroid dehydrogenase (HSDH) activity, as determined by mass spectrometry of thin layer chromatography (TLC) separated metabolites of primary and secondary bile acids. Incubation of E. lenta oxo-bile acid and iso-bile acid metabolites with whole-cells of the high-activity bile acid 7?-dehydroxylating bacterium, Clostridium scindens VPI 12708, resulted in minimal conversion of oxo-derivatives to lithocholic acid (LCA). Further, Iso-chenodeoxycholic acid (iso-CDCA; 3?,7?-dihydroxy-5?-cholan-24-oic acid) was not metabolized by C. scindens. We then located a gene encoding a novel 12?-HSDH in E. lenta DSM 2243, also encoded by strain C592, and the recombinant purified enzyme was characterized and substrate-specificity determined. Genomic analysis revealed genes encoding an Rnf complex (rnfABCDEG), an energy conserving hydrogenase (echABCDEF) complex, as well as what appears to be a complete Wood-Ljungdahl pathway. Our prediction that by changing the gas atmosphere from nitrogen to hydrogen, bile acid oxidation would be inhibited, was confirmed. These results suggest that E. lenta is an important bile acid metabolizing gut microbe and that the gas atmosphere may be an important and overlooked regulator of bile acid metabolism in the gut.
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