Functional groups matter: metabolomics analysis of Escherichia coli exposed to trans-cinnamic acid and its derivatives unveils common and unique targets

by Selleckchem | Feb 04 2024

Phenolic acids are derivatives of benzoic and cinnamic acids, which possess important biological activities at certain concentrations. Trans-cinnamic acid (t-CA) and its derivatives, such as p-coumaric acid (p-CA) and ferulic acid (FA) have been shown to have antibacterial activity against various Gram-positive and -negative bacteria. However, there is limited information available concerning the antibacterial mode of action of these phenolic acids. In this study, we aimed to ascertain metabolic alterations associated with exposure to t-CA, p-CA, and FA in Escherichia coli BW25113 using a nuclear magnetic resonance (NMR)-based metabolomics approach. The results showed that t-CA, p-CA, and FA treatments led to significant changes (p < 0.05) in the concentration of 42, 55, and 74% of the identified metabolites in E. coli, respectively. Partial least-squares discriminant analysis (PLS-DA) revealed a clear separation between control and phenolic acid groups with regard to metabolic response. Moreover, it was found that FA and p-CA treatment groups were clustered closely together but separated from the t-CA treatment group. Arginine, putrescine, cadaverine, galactose, and sucrose had the greatest impact on group differentiation. Quantitative pathway analysis demonstrated that arginine and proline, pyrimidine, glutathione, and galactose metabolisms, as well as aminoacyl-tRNA and arginine biosyntheses, were markedly affected by all phenolic acids. Finally, the H2O2 content of E. coli cells was significantly increased in response to t-CA and p-CA whereas all phenolic acids caused a dramatic increase in the number of apurinic/apyrimidinic sites. Overall, this study suggests that the metabolic response of E. coli cells to t-CA is relatively different from that to p-CA and FA. However, all phenolic acids had a certain impact on oxidative/antioxidant status, genomic stability, arginine-related pathways, and nucleic acid metabolism.

Comments:

This study delves into the effects of trans-cinnamic acid (t-CA), p-coumaric acid (p-CA), and ferulic acid (FA) on Escherichia coli BW25113 using a metabolomics approach. Here's a breakdown of the findings:

### Metabolite Changes:
- **t-CA, p-CA, and FA** caused significant alterations in the concentration of identified metabolites in E. coli.
- The percentages of altered metabolites were **42%, 55%, and 74%** for t-CA, p-CA, and FA, respectively.

### Analysis Techniques:
- **Partial least-squares discriminant analysis (PLS-DA)** showed distinct metabolic responses between control and phenolic acid-treated groups.
- **Group Clustering**: FA and p-CA treatment groups clustered closely together but were distinct from the t-CA treatment group.
- **Key Metabolites Impacting Differentiation**: Arginine, putrescine, cadaverine, galactose, and sucrose significantly influenced group separation.

### Pathway Analysis:
- **Affected Metabolic Pathways**: Arginine and proline, pyrimidine, glutathione, and galactose metabolisms, along with aminoacyl-tRNA and arginine biosyntheses, were notably impacted by all three phenolic acids.

### Biological Responses:
- **Oxidative/Antioxidant Status**: t-CA and p-CA increased H2O2 content in E. coli cells, indicating an impact on oxidative stress.
- **Genomic Stability**: All phenolic acids caused a substantial increase in the number of apurinic/apyrimidinic sites, suggesting an influence on genomic stability.

### Conclusion:
- **Distinct Metabolic Responses**: The metabolic reaction of E. coli cells to t-CA differed notably from p-CA and FA.
- **Common Impacts**: All phenolic acids influenced oxidative/antioxidant status, genomic stability, arginine-related pathways, and nucleic acid metabolism to varying extents.

This research highlights the multifaceted impact of these phenolic acids on bacterial metabolism and cellular processes, providing valuable insights into their potential antibacterial mechanisms and effects on bacterial physiology.