Abstract
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.
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The data that support the findings of this study are available from the corresponding author, ESE, on reasonable request.
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Funding
This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK Grant #: 118Z584), and the National Research Foundation of Korea (NRF Grant #: NRF-2018K2A9A1A06065371 and NRF-2021R1F1A1046500).
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The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Details of the contributions of each author: Design (ESE, BÇ, ŞSÇ) and supervision (ESE, BÇ, YKC) of the study, antibacterial activity assays (KAO, HÖ), phenolic acid treatments of E. coli cells and extractions of metabolites (KAO, HÖ, EY), preparation of NMR samples and NMR data acquisition (HK, YKC), NMR data processing (ESE), Chenomx analysis of NMR data (ESE, KAO, HÖ, EY), DNA damage analysis (GG, ESE), H2O2 measurement (GG, ŞSÇ, ESE), statistical analysis of the data (ESE, ŞSÇ), evaluation and interpretation of results (ESE, ŞSÇ, YKC, BÇ), preparation of figures and tables (ESE), drafting (ESE, KAO, ŞSÇ) and revision (all authors) of the manuscript.
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Onat-Taşdelen, K.A., Öztürkel-Kabakaş, H., Yüksektepe, E. et al. Functional groups matter: metabolomics analysis of Escherichia coli exposed to trans-cinnamic acid and its derivatives unveils common and unique targets. World J Microbiol Biotechnol 40, 47 (2024). https://doi.org/10.1007/s11274-023-03841-8
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DOI: https://doi.org/10.1007/s11274-023-03841-8