The type III secretion system (T3SS) is a major virulence factor in many Gram-negative bacterial pathogens and represents a particularly appealing target for antimicrobial agents. Previous studies have shown that the plant phenolic compound p-coumaric acid (PCA) plays a role in the inhibition of T3SS expression of the phytopathogen Dickeya dadantii 3937. This study screened a series of derivatives of plant phenolic compounds and identified that trans-4-hydroxycinnamohydroxamic acid (TS103) has an eight-fold higher inhibitory potency than PCA on the T3SS of D. dadantii. The effect of TS103 on regulatory components of the T3SS was further elucidated. Our results suggest that TS103 inhibits HrpY phosphorylation and leads to reduced levels of hrpS and hrpL transcripts. In addition, through a reduction in the RNA levels of the regulatory small RNA RsmB, TS103 also inhibits hrpL at the post-transcriptional level via the rsmB-RsmA regulatory pathway. Finally, TS103 inhibits hrpL transcription and mRNA stability, which leads to reduced expression of HrpL regulon genes, such as hrpA and hrpN. To our knowledge, this is the first inhibitor to affect the T3SS through both the transcriptional and post-transcriptional pathways in the soft-rot phytopathogen D. dadantii 3937.
Keywords: Rsm system; T3SS inhibitor; plant phenolic compound; two-component signal transduction system; type III secretion system.
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