Dataset Information

Genome-scale metabolic modeling of the human gut bacterium Bacteroides fragilis strain 638R.

ABSTRACT: Bacteroides fragilis is a universal member of the dominant commensal gut phylum Bacteroidetes. Its fermentation products and abundance have been linked to obesity, inflammatory bowel disease, and other disorders through its effects on host metabolic regulation and the immune system. As of yet, there has been no curated systems-level characterization of B. fragilis' metabolism that provides a comprehensive analysis of the link between human diet and B. fragilis' metabolic products. To address this, we developed a genome-scale metabolic model of B. fragilis strain 638R. The model iMN674 contains 1,634 reactions, 1,362 metabolites, three compartments, and reflects the strain's ability to utilize 142 metabolites. Predictions made with this model include its growth rate and efficiency on these substrates, the amounts of each fermentation product it produces under different conditions, and gene essentiality for each biomass component. The model highlights and resolves gaps in knowledge of B. fragilis' carbohydrate metabolism and its corresponding transport proteins. This high quality model provides the basis for rational prediction of B. fragilis' metabolic interactions with its environment and its host.

SUBMITTER: Neal M

PROVIDER: S-EPMC10635569 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Genome-scale metabolic modeling of the human gut bacterium Bacteroides fragilis strain 638R.

Neal Maxwell M Thiruppathy Deepan D Zengler Karsten K

PLoS computational biology 20231030 10

Bacteroides fragilis is a universal member of the dominant commensal gut phylum Bacteroidetes. Its fermentation products and abundance have been linked to obesity, inflammatory bowel disease, and other disorders through its effects on host metabolic regulation and the immune system. As of yet, there has been no curated systems-level characterization of B. fragilis' metabolism that provides a comprehensive analysis of the link between human diet and B. fragilis' metabolic products. To address thi ...[more]

PMID: 37903176

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Project description:Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT) of virulence genes and differential transcription of endogenous genes are clearly involved. The CRISPR-Cas system is a multi-functional system described in prokaryotes that may be involved in control both of HGT and of gene regulation. Results: Clustered regularly interspaced short palindromic repeats (CRISPR) elements in all strains of B. fragilis (n = 109) with publically available genomes were identified. Three different CRISPR-Cas types, corresponding most closely to Type IB, Type IIIB, and Type IIC, were identified. Thirty-five strains had two CRISPR-Cas types, and three strains included all three CRISPR-Cas types in their respective genomes. The cas1 gene in the Type IIIB system encoded a reverse-transcriptase/Cas1 fusion protein rarely found in prokaryotes. We identified a short CRISPR (3 DR) with no associated cas genes present in most of the isolates; these CRISPRs were found immediately upstream of a hipA/hipB operon and we speculate that this element may be involved in regulation of this operon related to formation of persister cells during antimicrobial exposure. Also, blood isolates of B. fragilis did not have Type IIC CRISPR-Cas systems and had atypical Type IIIB CRISPR-Cas systems that were lacking adjacent cas genes. Conclusions: This is the first systematic report of CRISPR-Cas systems in a wide range of B. fragilis strains from a variety of sources. There are four apparent CRISPR-Cas systems in B. fragilis-three systems have adjacent cas genes. Understanding CRISPR/Cas function in B. fragilis will elucidate their role in gene expression, DNA repair and ability to survive exposure to antibiotics. Also, based on their unique CRISPR-Cas arrays, their phylogenetic clustering and their virulence potential, we are proposing that blood isolates of B. fragilis be viewed a separate subgroup.

Dataset Information

Genome-scale metabolic modeling of the human gut bacterium Bacteroides fragilis strain 638R.

Publications

Genome-scale metabolic modeling of the human gut bacterium Bacteroides fragilis strain 638R.

Similar Datasets

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