# Innovation and Application of the Type III Secretion System Inhibitors in Plant Pathogenic Bacteria
## 3 Discovery of T3 SS Inhibitors in Plant Pathogens and Their Regulatory Mechanisms
### Plant Phenolic Compounds as T3 SS Inhibitors
amylovora_ with benzoic acid or 4-methoxy-cinnamic acid reduced the HR development in _Nicotiana tabacum_ cv. Xanthi leaves, suggesting that both phenolic compounds are functionally inhibiting T3 SS _in planta_. Earlier studies on phenylpropanol metabolism in _Vanilla planifolia_ have reported that 4-methoxy-cinnamic acid is one of the intermediates in the biosynthetic conversion of cinnamic acid to benzoic acid [130]. Benzoic acid could be produced via the conversion of \(t\)-cinnamic acid to salicylic acid [131]. _X. oryzae_ pv. _oryzae_ is the causal agent of bacterial blight, one of the major rice diseases in the world. _X. oryzae_ pv. _oryzae_ is the causal agent of bacterial blight, one of the major rice diseases in the world. _X. oryzae_ pv. _oryzicola_, which causes the bacterial leaf streak disease, is another rice pathogen [132]. Both pathogens process a T3 SS encoded by the group II _hrp_ gene clusters, in which HrpG and HrpX are two key regulators [16; 21; 30; 133]. HrpG is a response regulator of the OmpR family of TCSTS, which positively regulates the expression of _hrpX_. HrpX is an AraC family transcriptional regulator responsible for activating the transcription of _hrp_ genes [21; 133]. By combining the transcriptional screening of the T3 SS genes and HR assay in tobacco, [PERSON] et al. identified four plant phenolic compounds, including \(o\)-coumaric acid, _trans_-2-methoxycinnamic acid, _trans_-2-phenylcyclopropane-1-carboxylic acid, and _trans_-2-methylcinnamic acid, actively inhibited the T3 SS gene expression in vitro likely through the HrpG-HrpX regulatory cascade. Application of these T3 SS inhibitors reduced the HR of _X. oryzae_ pv. _oryzae_ in non-host plants and the water soaking and disease symptoms of the pathogen in rice [116]. Since no impact on other virulence factors of _X. oryzae_ pv. _oryzae_, such as the type II secretion system (T2 SS), exopolysaccharideacharide (EPS), and lipopolysaccharideacharide (LPS) [134; 135], was observed, the reduced virulence caused by the plant phenolic compounds in _X. oryzae_ pv. _oryzae_ is T3 SS-dependent. A recent study was conducted to further understand the response of _X. oryzae_ pv. _oryzae_ to \(o\)-coumaric acid using transcriptomic analysis [136]. In _R. solanacearum_, the bacterial wilt pathogen of tomato, much progress has been made in identifying coumarins as T3 SS inhibitors. Coumarins, consisting of fused benzene and \(\alpha\)-pyrone rings, are a family of plant-derived secondary metabolites containing a large class of phenolic substances [137]. Members of the coumarins have been extensively studied mainly for their antimicrobial properties [138]. Umbelliferone is a 7-hydroxycoumarin that has recently been reported to repress the expression of _hrpG_ and multiple T3 SS regulon genes in _R. solanacearum_[119; 120]. It reduced biofilm formation and suppressed the wilting disease process by reducing the colonization and proliferation of _R. solanacearum in planta_[120]. Besides, six plant phenolic compounds and derivatives, including _p_-coumaric acid, that repress the T3 SS in _D. dadantiti_, failed to modulate the expression of _R. solanacearum_ T3 SS genes [122].