Direct Binding of Salicylic Acid to Pectobacterium N-Acyl-Homoserine Lactone Synthase

Janak Raj Joshi, Netaly Khazanov, Nirmal Khadka, Amy O. Charkowski, Saul Burdman, Nir Carmi, Iris Yedidia, Hanoch Senderowitz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Salicylic acid (SA) is a hormone that mediates systemic acquired resistance in plants. We demonstrated that SA can interfere with group behavior and virulence of the soft-rot plant pathogen Pectobacterium spp. through quorum sensing (QS) inhibition. QS is a population density-dependent communication system that relies on the signal molecule acyl-homoserine lactone (AHL) to synchronize infection. P. parmentieri mutants, lacking the QS AHL synthase (expI-) or the response regulator (expR-), were used to determine how SA inhibits QS. ExpI was expressed in DH5α, the QS negative strain of Escherichia coli, revealing direct interference of SA with AHL synthesis. Docking simulations showed SA is a potential ExpI ligand. This hypothesis was further confirmed by direct binding of SA to purified ExpI, shown by isothermal titration calorimetry and microscale thermophoresis. Computational alanine scanning was employed to design a mutant ExpI with predicted weaker binding affinity to SA. The mutant was constructed and displayed lower affinity to the ligand in the binding assay, and its physiological inhibition by SA was reduced. Taken together, these data support a likely mode of action and a role for SA as potent inhibitor of AHL synthase and QS.

Original languageEnglish
Pages (from-to)1883-1891
Number of pages9
JournalACS Chemical Biology
Volume15
Issue number7
DOIs
StatePublished - 17 Jul 2020

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Copyright © 2020 American Chemical Society.

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