WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Metabolic Responses to Benzoic Acid Stress and Glutamine Transport-Dependent Vulnerabilities in Escherichia Coli Revealed by NMR Metabolomics(Springer, 2026) Yuksektepe, Ecem; Elgin, Emine Sonay; Onat-Tasdelen, Kadriye Aslihan; Chae, Young Kee; Dogu, Eralp; Catav, Sukru Serter; Ozturkel-Kabakas, HaticeBenzoic acid (BA) is a widely used weak organic acid preservative with antimicrobial activity, yet the metabolic basis of its antibacterial action and the determinants of bacterial sensitivity remain incompletely understood. Here we combined growth assays with H-1 NMR metabolomics to characterize BA-induced metabolic responses in Escherichia coli BW25113 and to examine metabolic changes associated with impaired glutamine transport. Wild-type BW25113 and its BA-sensitive isogenic Delta glnP mutant, lacking the membrane-bound glutamine permease of the high-affinity GlnHPQ transport system, were exposed to sublethal BA concentrations. BA slowed growth and significantly altered the levels of 42 metabolites in the wild-type and 38 in Delta glnP, with the mutant showing stronger growth inhibition and reduced BA tolerance. Both strains exhibited metabolic changes consistent with cellular responses to oxidative and acid stress, including alterations in central carbon metabolism, lysine degradation, cysteine and methionine metabolism, pyrimidine metabolism, and one-carbon pool by folate. However, several metabolic responses differed between the two strains. In wild-type cells, BA exposure was associated with changes in glycerolipid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, lysine biosynthesis, glycine, serine and threonine metabolism, and purine metabolism. In contrast, Delta glnP cells showed distinct alterations in D-amino acid metabolism, arginine biosynthesis, and other carbon fixation pathways. In addition, the mutant displayed substantial baseline differences relative to the wild-type, including altered nucleotide and amino acid pools. Together, these results indicate that both BA exposure and deletion of glnP induce broad metabolic adjustments in Escherichia coli. Loss of glnP is associated with distinct metabolic states and altered responses to BA stress, highlighting the importance of glutamine transport in adaptation to weak organic acid stress.Article Citation - WoS: 8Citation - Scopus: 8Functional Groups Matter: Metabolomics Analysis of <i>escherichia Coli</I> Exposed To Trans-Cinnamic Acid and Its Derivatives Unveils Common and Unique Targets(Springer, 2024) Onat-Tasdelen, Kadriye Aslihan; Ozturkel-Kabakas, Hatice; Yuksektepe, Ecem; Catav, Sukru Serter; Guzel, Gulnur; Col, Bekir; Elgin, Emine SonayPhenolic 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.