Type III secretion inhibitors for the management of bacterial plant diseases

Secretion systems are essential for phytopathogenic bacteria to produce surface structures for adhesion, aggregation and bacterial motility, as well as to secrete cell wall-degrading enzymes, proteases, toxins and effectors to defeat and reprogram host cells (Chang et al., 2014). In general, bacterial protein secretion apparatuses can be divided into different classes, based on their structures, functions and specificity. Among seven type secretion systems, Type III secretion system (T3SS) play major role disease development and pathogenesis. This system secreted substrates called effector proteins (Green and Mecsas, 2015). The T3SS is an attractive target for antimicrobial compounds as it is essential for virulence in many pathogenic gram negative bacteria. This system injects bacterial effector proteins into host cells to subvert their defences. T3SS-targeting small-molecule inhibitors have been discovered; these inhibitors prevent the bacteria from injecting effector proteins and from causing pathophysiology in host cells (Puigvert et al., 2019).

Screened nine plant extracts and 12 isolated compounds including molecules effective against human pathogens for their capacity to inhibit the T3SS of plant pathogens. Screening was performed by using a luminescent reporter system developed in the model pathogenic bacterium Ralstonia solanacearum. Five synthetic molecules, one natural product and two plant extracts were found to down-regulate T3SS transcription, most through the inhibition of the regulator hrpB. These candidate virulence inhibitors were then tested for their ability to protect plants and demonstrated that salicylidene acylhydrazides can limit R. solanacearum multiplication in planta and protect tomato plants from bacterial speck caused by Pseudomonas syringae pv. tomato (Puigvert et al., 2019).

Tao et al. (2019) conducted an experiments to know the effects of natural compounds on the T3SS of Xanthomonas oryzae pv. oryzae. Three of 34 compounds significantly inhibited the promoter activity of the harpin gene, hpa1, and were further checked for their impact on bacterial growth and on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results indicated that treatment of Xoo with CZ-1, CZ-4 and CZ-9 resulted in an obviously attenuated HR without affecting bacterial growth and survival. Moreover, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that the expression of the Xoo T3SS was suppressed by treatment with the three inhibitors.

Identified potential anti-virulence drugs against X. oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc) pathogens and screened a library of plant phenolic compounds and derivatives for their effects on the Xoo T3SS. Ten of 56 compounds significantly inhibited the promoter activity of a harpin gene, hpa1. These inhibitors were further tested for their impact on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results showed that pretreatment of Xoo with TS006 (o-coumaric acid, OCA), TS010, TS015 and TS018 resulted in significantly attenuated HR without affecting bacterial growth or survival (Fan et al., 2017).

Use of type III secretion system (T3SS) inhibitors is common in folk medicine for the treatment of bacterial infection. They have a great activity in inhibiting the bacterial type III secretion system (T3SS) and thereby mitigate bacterial pathogenesis. The mechanisms of action of these compounds is still unclear. Type III secretion system (T3SS) inhibitors constitute a promising tool for the management of bacterial diseases. Hence, type III secretion system (T3SS) inhibitors can be considered a promising novel strategy to deal with bacterial pathogens.

SELECTED REFERENCES:

FAN, S., TIAN, F., JIANYU, L., HUTCHINS, W. I., CHEN, H., YANG, F., YUAN, X., CUI, Z., YANG, C. AND CHENYANG HE, C., 2017, Identification of phenolic compounds that suppress the virulence of Xanthomonas oryzae on rice via the type III secretion system. Mol. Plant Pathol., 18(4): 555-568. PUIGVERT, M., SOLE, M., LOPEZ-GARCIA, B., COLL, N., BEAT TIE, K., DAVIS, R., ELOFSSON, M. AND VALLS, M., 2019, Type III secretion inhibitors for the management of bacterial plant diseases. Mol. Plant Pathol., 20(1): 20-32. TAO, H., FAN, S., JIANG, S., XIANG, X., YAN, X., ZHANG, L. AND CUI, Z., 2019, Small molecule inhibitors specifically targeting the Type III secretion system of Xanthomonas oryzae on rice. Int. J. Mol. Sci., 20: 971-981.