Ellagic acid derivatives from Terminalia chebula Retz. increase the susceptibility of Pseudomonas aeruginosa to stress by inhibiting polyphosphate kinase

AimPolyphosphate kinase 1 (PPK1) plays an important role in virulence, antibiotic resistance and survival under stress conditions and, therefore, is an attractive therapeutic target to control infections caused by multiple drug resistant Pseudomonas aeruginosa. This study explores the PPK1 inhibiting activity of ellagic acid derivatives (EADs) from Terminalia chebula Retz. that could increase the susceptibility of Ps.aeruginosa to in vitro stress conditions. Methods and ResultsEADs reduced ppk1 gene expression by 93% (P<005) and completely inhibited its activity (P<001) at 05mgml(-1). EADs-treated Ps.aeruginosa showed marked reduction in polyphosphate granules in cytosol. Expression of rpoS, the downstream master stress response regulator, was reduced by 94% (P<005) and the sensitivity of Ps.aeruginosa increased many fold to desiccation, oxidative (H2O2) and antibiotic (piperacillin) stresses. PPK-regulated swimming, swarming and twitching motilities and biofilm formation were also reduced significantly (P005) in MPAO1 and the clinical strains of Ps.aeruginosa. ConclusionEADs from T.chebula inhibited PPK1 expression and its activity and increased the sensitivity of Ps.aeruginosa to desiccation and oxidative stress while reducing tolerance to piperacillin. Significance and Impact of the StudyThe study underlines the potential of EADs as therapeutic agent against Ps.aeruginosa.