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

• Published in: Journal of applied microbiology Vol. 118; no. 4; pp. 817 - 825
• Main Authors: Sarabhai, S, Harjai, K, Sharma, P, Capalash, N
• Format: Journal Article
• Language: English
• Published: England Published for the Society for Applied Bacteriology by Blackwell Science 01-04-2015; Oxford University Press
• Subjects: Anti-Bacterial Agents - pharmacology; antibiotic resistance; Antibiotics; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; biofilm; cytosol; ellagic acid; Ellagic Acid - pharmacology; ellagic acid derivatives; Gene expression; granules; Humans; hydrogen peroxide; Kinases; motilities; oxidative stress; persister cells; Phosphotransferases (Phosphate Group Acceptor) - antagonists & inhibitors; Phosphotransferases (Phosphate Group Acceptor) - genetics; Phosphotransferases (Phosphate Group Acceptor) - metabolism; piperacillin; Plant Extracts - pharmacology; Polyphosphates - metabolism; ppk; Ps. aeruginosa; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - enzymology; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - physiology; rpoS; stress; stress response; Terminalia - chemistry; Terminalia chebula; virulence; stress; ellagic acid derivatives; motilities; rpoS; Terminalia chebula; Ps. aeruginosa; ppk; persister cells
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/jam.12733

AIM: Polyphosphate 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 RESULTS: EADs reduced ppk1 gene expression by 93% (P < 0·05) and completely inhibited its activity (P < 0·01) at 0·5 mg ml⁻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 < 0·05) 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 (P ≤ 0·05) in MPAO1 and the clinical strains of Ps. aeruginosa. CONCLUSION: EADs 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 STUDY: The study underlines the potential of EADs as therapeutic agent against Ps. aeruginosa.