The influence of cinnamic acid derivatives on the type III secretion system of Pseudomonas aeruginosa PAO1

Abstract:

[Objective] Pseudomonas aeruginosa, an opportunistic human pathogen, possesses a type III secretion system (TTSS) as one of the major virulence factors by which it secrets and translocates effector proteins into human host cells. In this study, five compounds which influence the expression of TTSS were identified from cinnamic acid derivatives. [Methods] The transcriptional reporter of exoS gene on plasmid pAT-exoS was used to monitor the exoS expression in the wild type strain PAO1 with the candidate compounds. [Results] Among 21 compounds, three compounds decreased the expression of exoS gene, whereas two compounds increased the expression of exoS gene. In addition, the compounds TS128, TS143 and TS160 showed inhibitory effect in bacterial growth. Western blot assay further showed that the level of ExoS was altered when the medium was added TS108 and TS165. The expression of exoS was partly restored to the wild-type when the plasmid p35-exsA which containing the exsA gene was introduced into PAO1. However, there is no difference of the exoS expression in the rsmY rsmZ double mutant with inhibitors TS108 and TS165. In addition, the production of N-Acyl homoserine lactones, which is positively regulated by the Gac/Rsm signaling pathway, is not affected with the inhibitors TS108 and TS165. [Conclusion] Our results suggest that the inhibitors TS108 and TS165 affect the expression of exoS through the transcriptional regulator ExsA instead of the Gac/Rsm regulatory pathway.

Key words:Pseudomonas aeruginosa, ExoS, Inhibitor, Inductor, Type III secretion system