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

Abstract

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 β-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 an- tibacterial 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 in- hibited violacein and pyocyanin production at 1/128 ×MIC. Additionally, QS autoinducers found in Chro- mobacterium 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 an- tibiofilm 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 β-lactamase activity in K. pneu- moniae . Conclusion: Results suggest that the anti-virulence potential of the extracts may be related to their ef- fect as extracellular autoinducer modulators. This study allowed to define potential applications of these extracts.