Deciphering the molecular mechanisms underlying anti-pathogenic potential of a polyherbal formulation Enteropan® against multidrug-resistant Pseudomonas aeruginosa.

IF 2 Q3 PHARMACOLOGY & PHARMACY
Drug Target Insights Pub Date : 2024-08-30 eCollection Date: 2024-01-01 DOI:10.33393/dti.2024.3082
Sweety Parmar, Gemini Gajera, Nidhi Thakkar, Hanmanthrao S Palep, Vijay Kothari
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引用次数: 0

Abstract

Objective: Anti-pathogenic potential of a polyherbal formulation Enteropan® was investigated against a multidrug-resistant strain of the bacterium Pseudomonas aeruginosa.

Methods: Growth, pigment production, antibiotic susceptibility, etc., were assessed through appropriate in vitro assays. Virulence of the test pathogen was assessed employing the nematode worm Caenorhabditis elegans as a model host. Molecular mechanisms underlining the anti-pathogenic activity of the test formulation were elucidated through whole transcriptome analysis of the extract-exposed bacterial culture.

Results: Enteropan-pre-exposed P. aeruginosa displayed reduced (~70%↓) virulence towards the model host C. elegans. Enteropan affected various traits like biofilm formation, protein synthesis and secretion, quorum-modulated pigment production, antibiotic susceptibility, nitrogen metabolism, etc., in this pathogen. P. aeruginosa could not develop complete resistance to the virulence-attenuating activity of Enteropan even after repeated exposure to this polyherbal formulation. Whole transcriptome analysis showed 17% of P. aeruginosa genome to get differentially expressed under influence of Enteropan. Major mechanisms through which Enteropan exerted its anti-virulence activity were found to be generation of nitrosative stress, oxidative stress, envelop stress, quorum modulation, disturbance of protein homeostasis and metal homeostasis. Network analysis of the differently expressed genes resulted in identification of 10 proteins with high network centrality as potential targets from among the downregulated genes. Differential expression of genes coding for five (rpoA, tig, rpsB, rpsL, and rpsJ) of these targets was validated through real-time polymerase chain reaction too, and they can further be pursued as potential targets by various drug discovery programmes.

破译多草药配方 Enteropan® 针对耐多药铜绿假单胞菌抗病原潜力的分子机制。
目的研究多草药配方 Enteropan® 对铜绿假单胞菌耐多药菌株的抗病潜力:方法:通过适当的体外试验评估生长、色素生成、抗生素敏感性等。以线虫秀丽隐杆线虫(Caenorhabditis elegans)为模式宿主,评估试验病原体的毒性。通过对提取物暴露的细菌培养物进行全转录组分析,阐明了试验配方抗病原活性的分子机制:结果:Enteropan 预暴露铜绿假单胞菌对模式宿主秀丽隐杆线虫的毒力降低(约 70%↓)。肠促胰素影响了该病原体的生物膜形成、蛋白质合成和分泌、定量调节色素产生、抗生素敏感性、氮代谢等多种性状。铜绿假单胞菌即使反复接触这种多草药制剂,也无法对 Enteropan 的毒力增强活性产生完全的抗性。全转录组分析表明,在 Enteropan 的影响下,17% 的铜绿假单胞菌基因组有不同表达。研究发现肠复安发挥其抗菌活性的主要机制是产生亚硝基应激、氧化应激、包膜应激、定量调节、蛋白质平衡紊乱和金属平衡紊乱。通过对不同表达基因的网络分析,从下调基因中确定了 10 个具有高网络中心性的蛋白质作为潜在靶标。实时聚合酶链式反应也验证了其中五个靶标(rpoA、tig、rpsB、rpsL 和 rpsJ)的编码基因的差异表达,可进一步将它们作为各种药物发现计划的潜在靶标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Drug Target Insights
Drug Target Insights PHARMACOLOGY & PHARMACY-
CiteScore
2.70
自引率
0.00%
发文量
5
审稿时长
8 weeks
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