Ruparel Feny J, Shah Siddhi K, Patel Jhanvi H, Thakkar Nidhi R, Gajera Gemini N, Kothari Vijay O
Institute of Science, Nirma University, Ahmedabad - India.
FJR, NRT, and GNG contributed equally.
Drug Target Insights. 2023 May 29;17:58-69. doi: 10.33393/dti.2023.2595. eCollection 2023 Jan-Dec.
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 and
Transcriptomes of and 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.
Genes associated with denitrification and sulfur metabolism emerged as the most important targets in . Increased buildup of nitrite (NO) in culture exposed to the polyherbal formulation was confirmed through 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 were the transcriptional regulator , immunoglobulin-binding protein Sbi, serine protease , the response regulator system, and gamma-hemolysin components and .
Further validation of the potential targets identified in this study is warranted through appropriate and assays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programs globally.
抗菌药物耐药性(AMR)是一个严重的全球威胁。迫切需要鉴定新的抗菌靶点,以助力抗菌药物研发项目。本研究尝试在两种重要病原体中鉴定潜在靶点。
对暴露于两种不同群体感应调节多草药配方的[病原体名称1]和[病原体名称2]的转录组进行网络分析,以鉴定连接度最高的差异表达基因(枢纽基因)作为潜在的抗毒力靶点。
与反硝化作用和硫代谢相关的基因成为[病原体名称1]中最重要的靶点。通过[检测方法名称]检测也证实,暴露于多草药配方[配方名称1]的[病原体名称1]培养物中亚硝酸盐(NO)积累增加。产生亚硝化应激和诱导硫饥饿似乎是针对这种臭名昭著的革兰氏阴性病原体的有效抗致病策略。在[病原体名称2]中鉴定出的重要靶点包括转录调节因子[调节因子名称]、免疫球蛋白结合蛋白Sbi、丝氨酸蛋白酶[蛋白酶名称]、双组分反应调节系统以及γ-溶血素组分[溶血素组分名称1]和[溶血素组分名称2]。
有必要通过在模型宿主中进行适当的[检测方法名称1]和[检测方法名称2]检测,对本研究中鉴定出的潜在靶点进行进一步验证。此类经过验证的靶点可能对全球众多抗菌药物研发项目至关重要。