Shahid Farah, Alghamdi Youssef Saeed, Mashraqi Mutaib, Khurshid Mohsin, Ashfaq Usman Ali
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
Department of Biology, Turabah University College, Taif University, P.O.BOX 11099, Taif 21944, Saudi Arabia.
Saudi J Biol Sci. 2022 Feb;29(2):1147-1159. doi: 10.1016/j.sjbs.2021.09.051. Epub 2021 Oct 1.
is one of the major causes of diarrhea and remained a critical microbe responsible for higher morbidity and mortality rates resulting from dysentery every year across the world. Antibiotic therapy of Shigella diseases plays a critical role in decreasing the prevalence as well as the fatality rate of this infection. However, the management of these diseases remains challenging, owing to the overall increase in resistance against many antimicrobials. The situation necessitates the rapid development of effective and feasible treatments. In the present study, the subtractive genomics approach was utilized to find the potential drug targets for strain Ss046. Various tools of bioinformatics were implemented to remove the human-specific homologous and pathogen-specific paralogous sequences from the bacterial proteome. Then, metabolic pathway and subcellular location analysis were performed of essential bacterial proteins to describe their role in various cellular processes. Only one essential protein i-e Chromosomal replication initiator protein DnaA was found in the proteome of the pathogen that could be used as a potent target for designing new drugs. 3D structure prediction of DnaA protein was carried out using Phyre 2. Molecular docking of 5000 phytochemicals was performed against DnaA to identify four top-ranked phytochemicals (Riccionidin A, Dothistromin, Fustin, and Morin) based on scoring functions and interaction with the active site. This study suggests that these phytochemicals could be used as antibacterial drugs to treat infections in the future. To confirm their efficacy and evaluate their drug potency, further in vitro analyses are required.
是腹泻的主要原因之一，并且仍然是一种关键微生物，每年在全球范围内导致痢疾引发更高的发病率和死亡率。志贺氏菌病的抗生素治疗在降低这种感染的患病率和死亡率方面发挥着关键作用。然而，由于对许多抗菌药物的耐药性总体增加，这些疾病的治疗仍然具有挑战性。这种情况需要迅速开发有效且可行的治疗方法。在本研究中，采用减法基因组学方法来寻找菌株Ss046的潜在药物靶点。运用各种生物信息学工具从细菌蛋白质组中去除人类特异性同源序列和病原体特异性旁系同源序列。然后，对必需细菌蛋白进行代谢途径和亚细胞定位分析，以描述它们在各种细胞过程中的作用。在病原体的蛋白质组中仅发现一种必需蛋白，即染色体复制起始蛋白DnaA，它可作为设计新药的有效靶点。使用Phyre 2对DnaA蛋白进行三维结构预测。针对DnaA对5000种植物化学物质进行分子对接，根据评分函数和与活性位点的相互作用确定四种排名靠前的植物化学物质（紫花地丁苷A、多节孢素、黄颜木素和桑色素）。本研究表明，这些植物化学物质未来可作为抗菌药物用于治疗感染。为了确认它们的疗效并评估它们的药物效力，还需要进一步的体外分析。
