Dataset Information

Phylogenetic investigation of Gammaproteobacteria proteins involved in exogenous long-chain fatty acid acquisition and assimilation.

ABSTRACT:

Background

The incorporation of exogenous fatty acids into the cell membrane yields structural modifications that directly influence membrane phospholipid composition and indirectly contribute to virulence. FadL and FadD are responsible for importing and activating exogenous fatty acids, while acyltransferases (PlsB, PlsC, PlsX, PlsY) incorporate fatty acids into the cell membrane. Many Gammaproteobacteria species possess multiple homologs of these proteins involved in exogenous fatty acid metabolism, suggesting the evolutionary acquisition and maintenance of this transport pathway.

Methods

This study developed phylogenetic trees based on amino acid and nucleotide sequences of homologs of FadL, FadD, PlsB, PlsC, PlsX, and PlsY via Mr. Bayes and RAxML algorithms. We also explored the operon arrangement of genes encoding for FadL. Additionally, FadL homologs were modeled via SWISS-MODEL, validated and refined by SAVES, Galaxy Refine, and GROMACS, and docked with fatty acids via AutoDock Vina. Resulting affinities were analyzed by 2-way ANOVA test and Tukey's post-hoc test.

Results

Our phylogenetic trees revealed grouping based on operon structure, original homolog blasted from, and order of the homolog, suggesting a more ancestral origin of the multiple homolog phenomena. Our molecular docking simulations indicated a similar binding pattern for the fatty acids between the different FadL homologs.

General significance

Our study is the first to illustrate the phylogeny of these proteins and to investigate the binding of various FadL homologs across orders with fatty acids. This study helps unravel the mystery surrounding these proteins and presents topics for future research.

SUBMITTER: Saksena S

PROVIDER: S-EPMC10439403 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Phylogenetic investigation of Gammaproteobacteria proteins involved in exogenous long-chain fatty acid acquisition and assimilation.

Saksena Saksham S Forbes Kwame K Rajan Nipun N Giles David D

Biochemistry and biophysics reports 20230704

<h4>Background</h4>The incorporation of exogenous fatty acids into the cell membrane yields structural modifications that directly influence membrane phospholipid composition and indirectly contribute to virulence. FadL and FadD are responsible for importing and activating exogenous fatty acids, while acyltransferases (PlsB, PlsC, PlsX, PlsY) incorporate fatty acids into the cell membrane. Many Gammaproteobacteria species possess multiple homologs of these proteins involved in exogenous fatty ac ...[more]

PMID: 37601446

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Project description:BackgroundGut microbial anaerobic fermentation produces short-chain fatty acids (SCFA), which are important substrates for energy metabolism and anabolic processes in mammals. SCFA can regulate the inflammatory response and increase the intestinal barrier integrity by enhancing the tight junction protein (TJp) functions, which prevent the passage of antigens through the paracellular space. The aim of this study was to evaluate the effect of in vitro supplementation with SCFA (acetate, propionate, butyrate, and lactate) at different concentrations on viability, nitric oxide (NO) release (oxidative stress parameter) in cell culture supernatants, and gene expression of TJp (occludin, zonula occludens-1, and claudin-4) and pro-inflammatory pathway-related mediators (β-defensin 1, TNF-α, and NF-κB) in intestinal porcine epithelial cell line J2 (IPEC-J2).ResultsThe SCFA tested showed significant effects on IPEC-J2, which proved to be dependent on the type and specific concentration of the fatty acid. Acetate stimulated cell viability and NO production in a dose-dependent manner (P < 0.05), and specifically, 5 mM acetate activated the barrier response through claudin-4, and immunity through β-defensin 1 (P < 0.05). The same effect on these parameters was shown by propionate supplementation, especially at 1 mM (P < 0.05). Contrarily, lactate and butyrate showed different effects compared to acetate and propionate, as they did not stimulate an increase of cell viability and regulated barrier integrity through zonula occludens-1 and occludin, especially at 30 mM and 0.5 mM, respectively (P < 0.05). Upon supplementation with SCFA, the increase of NO release at low levels proved not to have detrimental effects on IPEC-J2 proliferation/survival, and in the case of acetate and propionate, such levels were associated with beneficial effects. Furthermore, the results showed that SCFA supplementation induced β-defensin 1 (P < 0.05) that, in turn, may have been involved in the inhibition of TNF-α and NF-κB gene expression (P < 0.05).ConclusionsThe present study demonstrates that the supplementation with specific SCFA in IPEC-J2 can significantly modulate the process of barrier protection, and that particularly acetate and propionate sustain cell viability, low oxidative stress activity and intestinal barrier function.

Dataset Information

Phylogenetic investigation of Gammaproteobacteria proteins involved in exogenous long-chain fatty acid acquisition and assimilation.

Background

Methods

Results

General significance

Publications

Phylogenetic investigation of Gammaproteobacteria proteins involved in exogenous long-chain fatty acid acquisition and assimilation.

Similar Datasets

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