Multidrug-Resistant Escherichia coli Antagonized by Luteolin: A Mechanistic Insight into Virulence Suppression and Gut Microbiota Restoration
Abstract
Multidrug-resistant Escherichia coli (MDR-E. coli) poses a serious threat in foodborne infections, highlighting an urgent need for novel antimicrobial strategies. Natural plant-derived compounds, particularly flavonoids, have gained attention for their potential as alternative antimicrobial agents. This study aimed to evaluate the antibacterial efficacy and underlying mechanisms of luteolin (LUT), a dietary flavonoid, against MDR-E. coli, and to assess its immunomodulatory and microbiota-regulatory effects in vivo. (1) Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays were performed. (2) Biofilm formation, ATP synthesis, and alkaline phosphatase (AKP) leakage were measured. (3) Gene expression of resistance (tolC, ant(3″)-Ia) and virulence (fliC, K99, stx1) factors was analyzed via RT-PCR. (4) Network pharmacology and molecular docking identified key targets and pathways. (5) In vivo effects on intestinal pathology, inflammatory cytokines (IL-1β, IL-6, TNF-α), and gut microbiota composition were examined. The results show that (1) LUT exhibited potent antibacterial activity against MDR-E. coli (MIC = 1 mg/mL, MBC = 2 mg/mL). (2) It significantly inhibited biofilm formation, disrupted bacterial cell integrity, and suppressed ATP synthesis. (3) Expression of key resistance and virulence genes was downregulated. (4) In vivo, LUT alleviated intestinal inflammation, reduced pro-inflammatory cytokine levels, and restored gut microbial…
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