{"title":"利用基因组数据挖掘和蛋白-蛋白相互作用破译伤寒沙门氏菌生物膜中的靶蛋白级联","authors":"Aditya Upadhyay, Dharm Pal, Awanish Kumar","doi":"10.2174/1389202924666230815144126","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong><i>Salmonella typhi</i> biofilm confers a serious public health issue for lengthy periods and the rise in antibiotic resistance and death rate. Biofilm generation has rendered even the most potent antibiotics ineffective in controlling the illness, and the <i>S</i>. <i>typhi</i> outbreak has turned into a fatal disease typhoid. <i>S. typhi</i> infection has also been connected to other deadly illnesses, such as a gall bladder cancer. The virulence of this disease is due to the interaction of numerous genes and proteins of <i>S</i>. <i>typhi</i>.</p><p><strong>Objective: </strong>The study aimed to identify a cascade of target proteins in <i>S. typhi</i> biofilm condition with the help of genomic data mining and protein-protein interaction analysis.</p><p><strong>Methods: </strong>The goal of this study was to notice some important pharmacological targets in <i>S. typhi.</i> using genomic data mining, and protein-protein interaction approaches were used so that new drugs could be developed to combat the disease.</p><p><strong>Results: </strong>In this study, we identified 15 potential target proteins that are critical for <i>S. typhi</i> biofilm growth and maturation. Three proteins, CsgD, AdrA, and BcsA, were deciphered with their significant role in the synthesis of cellulose, a critical component of biofilm's extracellular matrix. The CsgD protein was also shown to have high interconnectedness and strong interactions with other important target proteins of <i>S. typhi</i>. As a result, it has been concluded that CsgD is involved in a range of activities, including cellulose synthesis, bacterial pathogenicity, quorum sensing, and bacterial virulence.</p><p><strong>Conclusion: </strong>All identified targets in this study possess hydrophobic properties, and their cellular localization offered proof of a potent therapeutic target. Overall results of this study, drug target shortage in <i>S. typhi</i> is also spotlighted, and we believe that obtained result could be useful for the design and development of some potent anti-salmonella agents for typhoid fever in the future.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662377/pdf/","citationCount":"0","resultStr":"{\"title\":\"Deciphering Target Protein Cascade in <i>Salmonella typhi</i> Biofilm using Genomic Data Mining, and Protein-protein Interaction.\",\"authors\":\"Aditya Upadhyay, Dharm Pal, Awanish Kumar\",\"doi\":\"10.2174/1389202924666230815144126\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong><i>Salmonella typhi</i> biofilm confers a serious public health issue for lengthy periods and the rise in antibiotic resistance and death rate. Biofilm generation has rendered even the most potent antibiotics ineffective in controlling the illness, and the <i>S</i>. <i>typhi</i> outbreak has turned into a fatal disease typhoid. <i>S. typhi</i> infection has also been connected to other deadly illnesses, such as a gall bladder cancer. The virulence of this disease is due to the interaction of numerous genes and proteins of <i>S</i>. <i>typhi</i>.</p><p><strong>Objective: </strong>The study aimed to identify a cascade of target proteins in <i>S. typhi</i> biofilm condition with the help of genomic data mining and protein-protein interaction analysis.</p><p><strong>Methods: </strong>The goal of this study was to notice some important pharmacological targets in <i>S. typhi.</i> using genomic data mining, and protein-protein interaction approaches were used so that new drugs could be developed to combat the disease.</p><p><strong>Results: </strong>In this study, we identified 15 potential target proteins that are critical for <i>S. typhi</i> biofilm growth and maturation. Three proteins, CsgD, AdrA, and BcsA, were deciphered with their significant role in the synthesis of cellulose, a critical component of biofilm's extracellular matrix. The CsgD protein was also shown to have high interconnectedness and strong interactions with other important target proteins of <i>S. typhi</i>. As a result, it has been concluded that CsgD is involved in a range of activities, including cellulose synthesis, bacterial pathogenicity, quorum sensing, and bacterial virulence.</p><p><strong>Conclusion: </strong>All identified targets in this study possess hydrophobic properties, and their cellular localization offered proof of a potent therapeutic target. Overall results of this study, drug target shortage in <i>S. typhi</i> is also spotlighted, and we believe that obtained result could be useful for the design and development of some potent anti-salmonella agents for typhoid fever in the future.</p>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2023-10-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662377/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.2174/1389202924666230815144126\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/1389202924666230815144126","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
伤寒沙门氏菌生物膜在很长一段时间内造成严重的公共卫生问题，并导致抗生素耐药性和死亡率上升。生物膜的产生使得即使是最有效的抗生素也无法控制这种疾病，伤寒沙门氏菌的爆发已经变成了一种致命的疾病伤寒。伤寒沙门氏菌感染也与其他致命疾病有关，比如胆囊癌。这种疾病的毒力是由于伤寒沙门氏菌的许多基因和蛋白质的相互作用。本研究旨在利用基因组数据挖掘和蛋白-蛋白相互作用分析方法，鉴定Typhi S. Typhi生物膜条件下的一系列靶蛋白。利用基因组数据挖掘和蛋白质-蛋白质相互作用的方法，可以开发新的药物来对抗这种疾病。在这项研究中，我们确定了15种潜在的靶蛋白，这些蛋白对伤寒沙门氏菌生物膜的生长和成熟至关重要。三种蛋白，CsgD, AdrA和BcsA，在生物膜细胞外基质的关键成分纤维素的合成中起着重要作用。CsgD蛋白还与伤寒沙门氏菌的其他重要靶蛋白具有高度的互联性和强相互作用。因此，已经得出结论，CsgD参与了一系列活动，包括纤维素合成，细菌致病性，群体感应和细菌毒力。本研究中所有确定的靶点都具有疏水特性，它们的细胞定位为有效的治疗靶点提供了证据。本研究的总体结果也突出了伤寒沙门氏菌的药物靶点短缺问题，我们相信所获得的结果可以为未来一些有效的抗伤寒沙门氏菌药物的设计和开发提供参考。
Deciphering Target Protein Cascade in Salmonella typhi Biofilm using Genomic Data Mining, and Protein-protein Interaction.
Background: Salmonella typhi biofilm confers a serious public health issue for lengthy periods and the rise in antibiotic resistance and death rate. Biofilm generation has rendered even the most potent antibiotics ineffective in controlling the illness, and the S. typhi outbreak has turned into a fatal disease typhoid. S. typhi infection has also been connected to other deadly illnesses, such as a gall bladder cancer. The virulence of this disease is due to the interaction of numerous genes and proteins of S. typhi.
Objective: The study aimed to identify a cascade of target proteins in S. typhi biofilm condition with the help of genomic data mining and protein-protein interaction analysis.
Methods: The goal of this study was to notice some important pharmacological targets in S. typhi. using genomic data mining, and protein-protein interaction approaches were used so that new drugs could be developed to combat the disease.
Results: In this study, we identified 15 potential target proteins that are critical for S. typhi biofilm growth and maturation. Three proteins, CsgD, AdrA, and BcsA, were deciphered with their significant role in the synthesis of cellulose, a critical component of biofilm's extracellular matrix. The CsgD protein was also shown to have high interconnectedness and strong interactions with other important target proteins of S. typhi. As a result, it has been concluded that CsgD is involved in a range of activities, including cellulose synthesis, bacterial pathogenicity, quorum sensing, and bacterial virulence.
Conclusion: All identified targets in this study possess hydrophobic properties, and their cellular localization offered proof of a potent therapeutic target. Overall results of this study, drug target shortage in S. typhi is also spotlighted, and we believe that obtained result could be useful for the design and development of some potent anti-salmonella agents for typhoid fever in the future.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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