5-Fluoroindole Inhibits Its Putative Target Methionine Synthase and Pseudomonas syringae pv. actinidiae Virulence

Chun Zhang1, Kunhong Zhao1, Zilin Wu1,2

  • 1State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Huaxi District, Guiyang 550025, China.

Insights

5-Fluoroindole effectively combats kiwifruit bacterial canker by killing Pseudomonas syringae pv. actinidiae (Psa). It disrupts bacterial membranes and targets the methionine synthase II (MetE) gene, offering a promising alternative to copper hydroxide treatments.

Area of Science:

  • Plant Pathology
  • Microbiology
  • Biochemistry

Background:

  • Bacterial canker, caused by Pseudomonas syringae pv. actinidiae (Psa), poses a significant threat to global kiwifruit production.
  • Current control methods, such as copper hydroxide, have limitations and raise environmental concerns.

Purpose of the Study:

  • To evaluate the bactericidal activity of 5-fluoroindole against Psa.
  • To elucidate the mechanism of action of 5-fluoroindole in Psa.
  • To explore the potential of 5-fluoroindole as a novel agent for controlling kiwifruit bacterial canker.

Main Methods:

  • Determination of half-maximal effective concentration (EC50) for 5-fluoroindole and copper hydroxide.
  • Assessment of membrane integrity, reactive oxygen species (ROS) accumulation, and apoptosis induction in Psa.
  • Transcriptome analysis to identify gene expression changes.
  • Microscale thermophoresis and isothermal titration calorimetry to study protein-ligand interactions.
  • Molecular docking to identify binding sites.

Main Results:

  • 5-Fluoroindole exhibited significant bactericidal activity against Psa (EC50 = 15.34 μg/mL), outperforming copper hydroxide (EC50 = 58.65 μg/mL).
  • 5-Fluoroindole induced membrane disruption, ROS accumulation, and apoptosis in Psa.
  • Treatment with 5-fluoroindole led to a 6.28-fold increase in methionine synthase II (MetE) gene expression.
  • Binding studies confirmed the interaction between 5-fluoroindole and MetE protein, with dissociation constants of 0.33 μM and 8.55 μM.
  • Molecular docking identified Asp693 as a key binding site, with no binding observed for the MetE D693A mutant.

Conclusions:

  • 5-Fluoroindole is a potent bactericide against Psa, demonstrating superior efficacy compared to copper hydroxide.
  • The mechanism of action involves membrane disruption, ROS generation, apoptosis induction, and specific binding to the MetE protein.
  • 5-Fluoroindole represents a promising candidate for developing novel strategies to manage kiwifruit bacterial canker.