Network analysis for identifying potential anti-virulence targets from whole transcriptome of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations.

IF 2 Q3 PHARMACOLOGY & PHARMACY
Drug Target Insights Pub Date : 2023-05-29 eCollection Date: 2023-01-01 DOI:10.33393/dti.2023.2595
Feny J Ruparel, Siddhi K Shah, Jhanvi H Patel, Nidhi R Thakkar, Gemini N Gajera, Vijay O Kothari
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引用次数: 0

Abstract

Introduction: Antimicrobial resistance (AMR) is a serious global threat. Identification of novel antibacterial targets is urgently warranted to help antimicrobial drug discovery programs. This study attempted identification of potential targets in two important pathogens Pseudomonas aeruginosa and Staphylococcus aureus.

Methods: Transcriptomes of P. aeruginosa and S. aureus exposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets.

Results: Genes associated with denitrification and sulfur metabolism emerged as the most important targets in P. aeruginosa. Increased buildup of nitrite (NO2) in P. aeruginosa culture exposed to the polyherbal formulation Panchvalkal was confirmed through in vitro assay too. Generation of nitrosative stress and inducing sulfur starvation seemed to be effective anti-pathogenic strategies against this notorious gram-negative pathogen. Important targets identified in S. aureus were the transcriptional regulator sarA, immunoglobulin-binding protein Sbi, serine protease SplA, the saeR/S response regulator system, and gamma-hemolysin components hlgB and hlgC.

Conclusion: Further validation of the potential targets identified in this study is warranted through appropriate in vitro and in vivo assays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programs globally.

Abstract Image

Abstract Image

Abstract Image

从暴露于某些抗病原多草药制剂的铜绿假单胞菌和金黄色葡萄球菌的全转录组中识别潜在抗病毒靶标的网络分析。
导言:抗菌药耐药性(AMR)是一个严重的全球性威胁。迫切需要鉴定新型抗菌靶标,以帮助抗菌药物研发计划。本研究试图鉴定两种重要病原体铜绿假单胞菌和金黄色葡萄球菌的潜在靶标:方法:对暴露于两种不同法定量调节多草药制剂的铜绿假单胞菌和金黄色葡萄球菌的转录组进行网络分析,以确定网络差异表达最高的基因(hubs)作为潜在的抗病毒靶标:结果:与反硝化和硫代谢相关的基因成为铜绿假单胞菌最重要的靶标。体外试验也证实,暴露于多草药制剂 Panchvalkal 的铜绿微囊藻培养物中亚硝酸盐(NO2)的积累增加。对这种臭名昭著的革兰氏阴性病原体来说,产生亚硝酸应激和诱导硫饥饿似乎是有效的抗病策略。在金黄色葡萄球菌中发现的重要靶标包括转录调节因子 sarA、免疫球蛋白结合蛋白 Sbi、丝氨酸蛋白酶 SplA、saeR/S 反应调节系统以及γ溶血素成分 hlgB 和 hlgC:结论:有必要通过在模型宿主体内进行适当的体外和体内试验,进一步验证本研究确定的潜在靶标。这些经过验证的靶点对全球许多抗菌药物发现项目至关重要。
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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