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利用消减基因组学鉴定无乳链球菌血清型V(ATCC BAA-611 / 2603 V/R)菌株中的药物靶点:一种计算机模拟方法。

Harnessing subtractive genomics for drug target identification in Streptococcus agalactiae serotype v (atcc baa-611 / 2603 v/r) strain: An in-silico approach.

作者信息

Chowdhury Ashiqur Rahman Khan, Tithi Farjana Yasmin, Bhuiyan Nusrat Zahan, Ishita Afsana Ferdousi, Sohel Md Mahmodul Hasan

机构信息

Department of Life Sciences, School of Environment and Life Sciences, Independent University, Bangladesh.

出版信息

PLoS One. 2025 Aug 21;20(8):e0319368. doi: 10.1371/journal.pone.0319368. eCollection 2025.

Abstract

Developing a therapeutic target for bacterial disease is challenging. In silico subtractive genomics methodology offer a promising alternative to traditional drug discovery methods. Streptococcus agalactiae infections depend on two crucial criteria: drug-resistance and the existence of virulence factors. It is essential to underline that S. agalactiae strains have emerged to be resistant to several drugs. Hence, there is a need for research on novel drugs and techniques that are potent, economical, productive, and dependable to combat S. agalactiae infections. In this study advanced computational techniques were exploited to examine potential druggable targets exclusive to this pathogen. Our study uncovered 200 non-homologous proteins in S. agalactiae serotype V (Strain ATCC BAA-611/ 2603 V/R) and identified 68 essential proteins indispensable for the bacterium's survival. Therefore, these 68 proteins are potential targets for drug development. Subcellular localization analysis unveiled that the pathogen's cytoplasmic membrane contained essential proteins among these vital non-homologous proteins. On the other hand, based on virulent protein predictions, six proteins were seen to be virulent. Among these, we prioritized two proteins (Sensor protein LytS and Galactosyl transferase CpsE which are exclusively found in S. agalactiae) as potential druggable targets and selected them for further structural investigation. The proteins chosen could serve as a foundation for the identification of a promising therapeutic compound that has the potential to neutralize these enzymatic proteins, thereby contributing to the reduction of risks linked to the drug-resistant S. agalactiae.

摘要

开发针对细菌性疾病的治疗靶点具有挑战性。计算机辅助减法基因组学方法为传统药物发现方法提供了一种有前景的替代方案。无乳链球菌感染取决于两个关键标准:耐药性和毒力因子的存在。必须强调的是,无乳链球菌菌株已出现对多种药物耐药的情况。因此,需要研究有效、经济、高效且可靠的新型药物和技术来对抗无乳链球菌感染。在本研究中,利用先进的计算技术来研究该病原体特有的潜在可成药靶点。我们的研究在无乳链球菌血清型V(菌株ATCC BAA - 611/2603 V/R)中发现了200种非同源蛋白,并鉴定出68种对该细菌生存不可或缺的必需蛋白。因此,这68种蛋白是药物开发的潜在靶点。亚细胞定位分析表明,在这些重要的非同源蛋白中,病原体的细胞质膜含有必需蛋白。另一方面,基于毒力蛋白预测,发现有6种蛋白具有毒力。其中,我们将两种蛋白(仅在无乳链球菌中发现的传感蛋白LytS和半乳糖基转移酶CpsE)优先作为潜在的可成药靶点,并选择它们进行进一步的结构研究。所选择的蛋白可为鉴定一种有前景的治疗化合物奠定基础,该化合物有可能中和这些酶蛋白,从而有助于降低与耐药性无乳链球菌相关的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0e/12370063/b112ad85ac29/pone.0319368.g001.jpg

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