Polyphenolic extracts from Diospyros kaki and Vitis vinifera by-products stimulate cytoprotective effects in bacteria-cell host interactions by mediation of transcription factor Nrf2.

BACKGROUND: The intestinal and skin epithelium play a strong role against bacterial stimuli which leads to inflammation and oxidative stress when overwhelmed. Polyphenols from fruit-rich diets and by-products show promise against bacterial deleterious effects; however, their antibacterial and health-promoting effects remain understudied. PURPOSE: This study aimed to assess the impact of polyphenolic extracts of grape (GrPE), persimmon (PePE) and pomegranate (PoPE) by-products on bacterial pathogen-host interactions, focusing beyond growth inhibition to explore their effects on bacterial adhesion, invasion, and modulation of host responses. METHODS: The microdilution method, as well as the tetrazolium based MTT cell proliferation and cytotoxicity assay with crystal violet staining were used to identify extracts sub-inhibitory concentrations that interfere with bacterial adhesion, invasion or lipopolysaccharides (LPS) effect on cell hosts without compromising host viability. The cytoprotective effects of extracts were assessed in a knock-down model of nuclear factor erythroid 2-related factor 2 (Nrf2). RESULTS: All extracts demonstrated significant reductions in pathogen adhesion to Caco-2 and HaCaT cells while preserving cellular integrity. Notably, PePE exhibited specific efficacy against Salmonella enterica adhesion, attributed mostly to its gallic acid content, whereas PoPE reduced S. enterica invasion in Caco-2 cells. The extracts supported the prevalence of non-pathogenic and commensal strains of intestinal and skin surfaces, selectively reducing pathogenic adhesion. The extracts mitigated the oxidative stress, enhanced the barrier function, and modulated the pro-inflammatory cytokines in LPS-challenged cells. GrPE, rich in anthocyanins, and PePE were found to mediate their protective effects through Nrf2 activation, while PoPE exerted multifaceted actions independent of Nrf2. CONCLUSION: Our results highlight the therapeutic potential of GrPE, PePE, and PoPE in shaping bacterial-host interactions, endorsing their utility as novel nutraceuticals for both oral and topical applications to prevent potential bacterial infections through innovative mechanisms.

Autoinducers modulation as a potential anti-virulence target of bacteria by phenolic compounds.

OBJECTIVE: The goal of this study was to determine the effects of phenolic extracts from grape (GrPE), pomegranate (PoPE), and persimmon (PePE) by-products on bacterial virulence activities such as biofilms, motility, energy-dependent efflux pumps, and ß-lactamase activity, which are modulated primarily by quorum sensing (QS), defining their potential applications. METHOD: The microdilution method was used to determine the minimum inhibitory concentration (MIC) and sub-inhibitory concentrations (SICs) of the extracts against reference pathogenic bacteria. The antibacterial mode of action was determined by labelling bacterial cells in in vivo cell-tracking experiments. RESULTS: Antibiograms showed that PoPE inhibited bacteria at lower concentrations, and PePE had a stronger effect against Klebsiella pneumoniae. Both extracts caused significant cell membrane damage (CMD), whereas GrPE did not. At SICs, all extracts showed anti-QS activity, especially PePE, which inhibited violacein and pyocyanin production at 1/128 × MIC. Additionally, QS autoinducers found in Chromobacterium violaceum and Pseudomonas aeruginosa were modulated by the extracts; PePE showed the highest modulation. Antibiofilm assays revealed that GrPE, at MIC and 2 × MIC, acted as a potent antibiofilm agent against biofilms of Pseudomonas putida, Bacillus cereus, and Staphylococcus aureus, which was related to disruption of swarming motility by GrPE. All extracts, especially PoPE, exerted a potent effect against the activation of efflux pumps of P. aeruginosa as well as ß-lactamase activity in K. pneumoniae. CONCLUSION: Results suggest that the anti-virulence potential of the extracts may be related to their effect as extracellular autoinducer modulators. This study allowed to define potential applications of these extracts.