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

Abstract

<i>Ralstonia solanacearum</i> 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 <i>R. solanacearum</i> for the purpose of developing new agrochemicals targeting this infection, here, we exploited a typical activity-based protein profiling technique for target discovery in <i>R. solanacearum</i> based on an activity-based probe <b>1</b> 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 <i>S</i>-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 <b>1</b> further confirmed that this protein was a target of oxadiazole sulfones. We anticipated that these discovered protein targets in <i>R. solanacearum</i> can stimulate the discovery and development of novel agrochemicals targeting bacterial infections caused by <i>R. solanacearum</i>.