Sarabhai S, Harjai K, Sharma P, Capalash N
Department of Microbiology, Panjab University, Chandigarh, India.
J Appl Microbiol. 2015 Apr;118(4):817-25. doi: 10.1111/jam.12733. Epub 2015 Feb 3.
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.
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 (H2 O2 ) 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.
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.
The study underlines the potential of EADs as therapeutic agent against Ps. aeruginosa.
多聚磷酸激酶1（PPK1）在毒力、抗生素耐药性及应激条件下的生存中发挥重要作用，因此是控制多重耐药铜绿假单胞菌所致感染的一个有吸引力的治疗靶点。本研究探索诃子中鞣花酸衍生物（EADs）的PPK1抑制活性，其可增加铜绿假单胞菌对体外应激条件的敏感性。
EADs在0.5 mg/ml时使ppk1基因表达降低93%（P<0.05），并完全抑制其活性（P<0.01）。经EADs处理的铜绿假单胞菌胞质中的多聚磷酸盐颗粒显著减少。下游主要应激反应调节因子rpoS的表达降低94%（P<0.05），铜绿假单胞菌对干燥、氧化（H2O2）和抗生素（哌拉西林）应激的敏感性增加了许多倍。在MPAO1和铜绿假单胞菌临床菌株中，PPK调节的游动、群集和颤动运动以及生物膜形成也显著减少（P≤0.05）。
诃子中的EADs抑制PPK1表达及其活性，增加铜绿假单胞菌对干燥和氧化应激的敏感性，同时降低对哌拉西林的耐受性。
该研究强调了EADs作为抗铜绿假单胞菌治疗剂的潜力。
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