Design and Synthesis of Mandelic Acid Derivatives for Suppression of Virulence via T3SS against Citrus Canker

J Agric Food Chem. 2024 May 1;72(17):9611-9620. doi: 10.1021/acs.jafc.3c07681. Epub 2024 Apr 22.

Abstract

Citrus canker, a highly contagious bacterial disease caused by Xanthomonas citri subsp. citri (Xcc), poses a substantial threat to citrus crops, leading to serious reductions in fruit yield and economic losses. Most commonly used bactericides against Xcc lead to the rapid development of resistant subpopulations. Therefore, it is imperative to create novel drugs, such as type III secretion system (T3SS) inhibitors, that specifically target bacterial virulence factors rather than bacterial viability. In our study, we designed and synthesized a series of mandelic acid derivatives including 2-mercapto-1,3,4-thiazole. Seven substances were found to reduce the level of transcription of hpa1 without affecting bacterial viability. In vivo bioassays indicated that compound F9 significantly inhibited hypersensitive response and pathogenicity. RT-qPCR assays showed that compound F9 visibly suppressed the expression of Xcc T3SS-related genes as well as citrus canker susceptibility gene CsLOB1. Furthermore, the combination with compound F9 and quorum-quenching bacteria HN-8 can also obviously alleviate canker symptoms.

Keywords: Xanthomonas citri subsp. citri (Xcc); citrus canker; mandelic acid derivatives; quorum quenching; type III secretion system (T3SS).

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Citrus* / chemistry
  • Citrus* / microbiology
  • Drug Design
  • Mandelic Acids* / chemistry
  • Mandelic Acids* / pharmacology
  • Plant Diseases* / microbiology
  • Type III Secretion Systems* / genetics
  • Virulence / drug effects
  • Xanthomonas* / drug effects
  • Xanthomonas* / pathogenicity

Substances

  • Mandelic Acids
  • Bacterial Proteins
  • Type III Secretion Systems
  • Anti-Bacterial Agents
  • mandelic acid

Supplementary concepts

  • Xanthomonas citri