4-aminobenzoic acid attenuates Ralstonia solanacearum virulence by suppressing quorum sensing system

Quorumsensing (QS) is widely involved in the regulation of the biological functions and pathogenic processesof bacteria in a cell density-dependent manner. The anthranilic acid signal is directly sensed by the receptor RaaR, a transcription regulator, to control the expression level of downstream target genesin Ralstonia solanacearum, thus affecting the QS signals generationand the bacterial virulence. Here, we reported that 4-aminobenzoic acid (PABA), a structural analogue of anthranilic acid, not only significantly inhibited the production of extracellular polysaccharides (EPS), biofilm formation and motility of R. solanacearum, but also reduced the expression level of QS signaling molecules. We also found that PABA can directly bind to the RaaR and prevented the binding of RaaR to the promoters of the target genes, which were related to the QS system and pathogenicity of R. solanacearum. The point mutations of RaaR at F137 and I270, abolished the binding between RaaR and PABA, indicating that these two amino acid residues may be crucial for the interaction between RaaR and PABA.These findings indicated that PABA could be a potent inhibitor of anthranilic acid signalingto interfere withthe QS systems of R. solanacearum to attenuate the pathogenicity. Together, our work presented a non-antibiotic-based treatment strategy and provide a theoretical basis for the development of novel antibacterial treatment.