Parmar Sweety, Gajera Gemini, Thakkar Nidhi, Palep Hanmanthrao S, Kothari Vijay
Institute of Science, Nirma University, Ahmedabad - India.
Dr. Palep's Medical Research Foundation, Mumbai - India.
Drug Target Insights. 2024 Aug 30;18:54-69. doi: 10.33393/dti.2024.3082. eCollection 2024 Jan-Dec.
Anti-pathogenic potential of a polyherbal formulation Enteropan® was investigated against a multidrug-resistant strain of the bacterium .
Growth, pigment production, antibiotic susceptibility, etc., were assessed through appropriate assays. Virulence of the test pathogen was assessed employing the nematode worm 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.
Enteropan-pre-exposed displayed reduced (~70%↓) virulence towards the model host . Enteropan affected various traits like biofilm formation, protein synthesis and secretion, quorum-modulated pigment production, antibiotic susceptibility, nitrogen metabolism, etc., in this pathogen. 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 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 (, , , , and ) 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.
研究多草药配方制剂Enteropan®对一种多重耐药细菌菌株的抗病原体潜力。
通过适当的检测评估生长、色素产生、抗生素敏感性等。以线虫作为模型宿主评估受试病原体的毒力。通过对提取物处理的细菌培养物进行全转录组分析，阐明受试制剂抗病原体活性的分子机制。
预先用Enteropan处理的菌株对模型宿主的毒力降低（约70%↓）。Enteropan影响该病原体的各种特性，如生物膜形成、蛋白质合成与分泌、群体感应调节的色素产生、抗生素敏感性、氮代谢等。即使反复接触这种多草药配方制剂，该菌株也无法对Enteropan的毒力减弱活性产生完全抗性。全转录组分析表明，在Enteropan的影响下，该菌株基因组的17%发生差异表达。发现Enteropan发挥其抗毒力活性的主要机制是产生亚硝化应激、氧化应激、包膜应激、群体感应调节、蛋白质稳态和金属稳态的紊乱。对差异表达基因的网络分析导致从下调基因中鉴定出10个具有高网络中心性的蛋白质作为潜在靶点。通过实时聚合酶链反应也验证了编码这些靶点中五个（、、、和）的基因的差异表达，并且各种药物发现计划可以进一步将它们作为潜在靶点进行研究。
