Alkyl Ferulate Esters as Multifunctional Food Additives: Antibacterial Activity and Mode of Action against Escherichia coli in Vitro

Abstract

This work aims to prepare ferulic acid alkyl esters (FAEs) through the lipase-catalyzed reaction between methyl ferulate and various fatty alcohols in deep eutectic solvents and ascertain their antibacterial activities and mechanisms. Screens of antibacterial effects of FAEs against Escherichia coli ATCC 25922 (E. coli) and Listeria monocytogenes ATCC 19115 (L. monocytogenes) revealed that hexyl ferulate (FAC6) exerted excellent bacteriostatic and bactericidal effects on E. coli and L. monocytogenes (minimum inhibitory concentration (MIC): 1.6 and 0.1 mM, minimum bactericidal concentration (MBC): 25.6 and 0.2 mM, respectively). The antibacterial mechanism of FAC6 against E. coli was systematically studied to facilitate its practical use as a food additive with multifunctionalities. The growth and time-kill curves implied the partial cell lysis and inhibition of the growth of E. coli caused by FAC6. The result related to propidium iodide uptake and cell constituents' leakage (K + , proteins, nucleotides, and β-galactosidase) implied that bacterial cytomembranes were substantially compromised by FAC6. Variations on morphology and cardiolipin microdomains and membrane hyperpolarization of cells visually verified that FAC6 induced cell elongation and destructed the cell membrane with cell wall perforation. SDS-PAGE analysis and alterations of fluorescence spectra of bacterial membrane proteins manifested that FAC6 caused significant changes in constitutions and conformation of membrane proteins. Furthermore, it also could bind to minor grooves of E. coli DNA to form complexes. Meanwhile, FAC6 exhibited antibiofilm formation activity. These findings indicated that that FAC6 has promising potential to be developed as a multifunctional food additive.

Synthesis, Antimicrobial Activity, Structure-Activity Relationship, and Molecular Docking Studies of Indole Diketopiperazine Alkaloids

“…Lipophilicity is an important factor for exploring the mechanism of action of antimicrobial agent against pathogenic bacteria (Shi et al, 2018). Therefore, the theoretical partition coefficients (Clog P ) were considered for the current discussion.…”

“…Moreover, low activity 5a−5e and 6a−6e had higher Clog P values (3.14–4.80). Shi et al have reported that ferulic acid and ferulic acid alkyl esters (FAC2) with 1.4212 and 2.1762 of Clog P values showed higher antibacterial activity against E. coli as compared with other similar compounds having higher Clog P values (Shi et al, 2018). Moreover, this similar trend also was reported by Wu et al They found auranofin analogs with lower log P values (1–2) exhibited better activity than some analogs with higher log P values (>3) against S. aureus, E. coli , and P. aeruginosa (Wu et al, 2019).…”

Synergetic Inactivation Mechanism of Protocatechuic Acid and High Hydrostatic Pressure against Escherichia coli O157:H7

“…However, the protein and nucleic acid leakage in the PCA + HHP group was less than that of HHP group ( Figure 2 A,B), which contradicted with PI-based results, in which the PCA + HHP treatment led to greater membrane permeability. According to Shi et al [ 27 ], a slight increase in permeability may lead to K + and Mg 2+ leakage, but protein and nucleic acid leakage would require severe membrane damage (such as holes in the membranes, which were found in the AFM results). The K + and Mg 2+ leakage levels, of the PCA + HHP group, were higher than those of the HHP group ( Figure 2 C,D).…”

“…The final concentration was determined by comparing and converting the absorbance with that of the standard protein solution (bovine serum albumin, 0.563 mg/mL). The intracellular nucleic acid content was determined at OD 260 nm using a UV-vis spectrophotometer in accordance with previous research [ 27 ] with modifications. The intracellular K + and Mg 2+ concentrations were determined using potassium [ 28 ] and magnesium assay kits [ 29 ], respectively, with slight modifications.…”

Recent advances in the enzymatic synthesis of lipophilic antioxidant and antimicrobial compounds

“…For instance, alkyl ferulates synthesized by esterification of the ferulic acid with alcohols of 4–12 carbon atoms in a molecule catalyzed by lipase B from C. antarctica were the subject of studies by Shi et al ( 2018 , 2019 ). Among the obtained compounds, hexyl ferulate (Fig.…”