Suppressing the suppressor: Gallic acid induced asymmetric tetramerization of the pleotropic virulence factor SuhB from Pseudomonas aeruginosa abolishes its extragenic suppressor activities. A structure-based functional study

Abstract

Pseudomonas aeruginosa SuhB (PaSuhB) is a member of the bacterial Inositol monophosphatase family proteins. Numerous scientific evidences suggest PaSuhB is the pleotropic regulator of different metabolic pathways involved in bacterial biofilm formation and virulence determination. In this study, we have solved the high-resolution crystal structures of PaSuhB in its apo and substrate (Inositol monophosphatase) bound forms. Moreover, we carried out 3D pharmacophore modelling of the bound substrate to identify gallic acid, a phyto-phenol, abundant in medicinal plants, as a novel PaSuhB inhibitor. The high-resolution crystal structure of gallic acid/PaSuhB binary complex leads to the identification of a novel allosteric ligand binding site of the protein. In vitro, gallic acid induces the cold-sensitive growth of P. aeruginosa and E. coli, the previously reported phenomenon observed in suhB deletion mutants and also inhibits the swimming motility of P. aeruginosa. The plausible anti-bacterial molecular mechanism of action of gallic acid is presented herein.