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

J Agric Food Chem. 2020 Feb 26;68(8):2340-2346. doi: 10.1021/acs.jafc.9b07192. Epub 2020 Feb 17.

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.

Keywords: ABPP; Ralstonia solanacearum; oxadiazole sulfones; target discovery.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Oxadiazoles / pharmacology*
  • Plant Diseases / microbiology*
  • Proteomics
  • Ralstonia solanacearum / drug effects*
  • Ralstonia solanacearum / genetics
  • Ralstonia solanacearum / metabolism
  • Sulfones / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Fungal Proteins
  • Oxadiazoles
  • Sulfones