Target Discovery in Ralstonia solanacearum through an Activity-Based Protein Profiling Technique Based on Bioactive Oxadiazole Sulfones

Abstract

Ralstonia solanacearum is an extremely destructive and rebellious phytopathogen that can cause bacterial wilt diseases in more than 200 plant species. To explore and discover the potential targets in R. solanacearum for the purpose of developing new agrochemicals targeting this infection, here, we exploited a typical activity-based protein profiling technique for target discovery in R. solanacearum based on an activity-based probe 1 derived from bioactive oxadiazole sulfones. A total of 65 specific targets were identified with high confidence through a quantitative chemical proteomic approach. Three representative proteins (glycine cleavage system H protein, thiol peroxidase, and dihydrolipoamide S-succinyltransferase) were validated as the targets by using the immunoblotting analysis with their respective antibodies. Additionally, the in vitro interaction between the recombinant thiol peroxidase and probe 1 further confirmed that this protein was a target of oxadiazole sulfones. We anticipated that these discovered protein targets in R. solanacearum can stimulate the discovery and development of novel agrochemicals targeting bacterial infections caused by R. solanacearum.

Chemical Composition, Antibacterial, Antioxidant and Enzyme Inhibitory Activities of the Essential Oil from Leaves of Psidium guajava L.

“…Diseases have continuously and significantly impacted crop yield. For instance, plant scab, bacterial wilt, and soft rot of plants have brought about the greatest economic losses in recent years [1–3] . More specifically, the typical bacteria that cause these diseases are Streptomyces acidiscabies ( S. acidiscabies ), Ralstonia solanacearum ( R. solanacearum ), and Erwinia carotovora subsp carotovora borgey ( E. carotovora subsp carotovora borgey) which affect plants, including potatoes, beets, carrots, and tomatoes [4–6] .…”

Discovery of Novel Dihydrolipoamide S-Succinyltransferase Inhibitors Based on Fragment Virtual Screening

“…DLST was found as the main target of JHXJZ in Xoo . JHXJZ may affect the cells by regulating the lysine succinyl modification level energy metabolism process [ 17 , 18 ]. The inhibitory activity of compound 10 on DLST was evaluated ( Figure 5 ).…”

“…The inhibitory activity of compound 10 against DLST was tested according to the previously reported method and the instructions of the enzyme activity kit [ 17 , 18 ]. The Xoo and Xoc bacteria solutions at the logarithmic growth period were added to the NB medium (5 mL) and shaken at 28 °C until the OD 600 value reached 0.3.…”

“…In our previous work, we found the sulfone candidate antibacterial agent JHXJZ [ 16 ]. Dihydrolipoamide S -succinyltransferase (DLST) was verified to be the target of JHXJZ by the click chemistry and quantitative chemical proteomic approach [ 17 , 18 ]. In this work, based on DLST, a model was established by rapidly identifying the non-effect fragments, thereby selectively replacing and optimizing the affinity of the drugs.…”

An Efficient Approach for Separating Essential Oil and Polysaccharides Simultaneously from Fresh Leaves of Guajava by Microwave-Mediated Hydrodistillation with Lithium Salts and Antibacterial Activity of Essential Oil

“…Diseases have continuously and significantly impacted crop yield. For instance, the economic losses caused by plant scab, bacterial wilt, and soft rot are the largest in recent years [15].…”