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基于整合生物信息学的消减基因组学方法,解析来自 XDR 伤寒沙门氏菌 H-58 株的假定蛋白的治疗功能。

Integrated bioinformatics based subtractive genomics approach to decipher the therapeutic function of hypothetical proteins from Salmonella typhi XDR H-58 strain.

机构信息

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

Lab 103, PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.

出版信息

Biotechnol Lett. 2022 Feb;44(2):279-298. doi: 10.1007/s10529-021-03219-6. Epub 2022 Jan 17.

Abstract

PURPOSE

The efficacy of drugs against Salmonella infection have compromised due to emerging XDR H58 strain. There is a dire need to find novel antimicrobial drug targets as well as drug candidates to cure by the XDR strain of Salmonella. It is observed that the complete genome sequence of the XDR H58 strain contains a large number of hypothetical proteins with unknown cellular and biological functions. Hence, it is indispensable to annotate these proteins functionally as well as structurally to identify novel drug targets.

METHODS

In the current study, a comparative genomics and proteomics based approach was applied to find the novel drug targets in XDR strain while comparing the MDR and NR strains of Salmonella typhi.

RESULTS

The characterization of ~ 350 hypothetical proteins were performed through determination of their physio-chemical properties, sub-cellular localization, functional annotation, and structure-based studies. As a result, only five proteins were prioritized as essential, druggable, and virulent proteins. Moreover, only one protein i.e. WP_000916613.1 was functionally annotated with high confidence and subjected to further structure-based analysis.

CONCLUSION

The current study presents a hypothetical protein from the XDR S. typhi proteome as a potential pharmacological target against which novel therapeutic candidates may be predicted. The outcome of the current study may lead to formulate a general set of pipelines for better understanding of the role of hypothetical proteins in pathogenesis of not only Salmonella but also for other pathogens.

摘要

目的

由于新兴的 XDR H58 菌株的出现,抗沙门氏菌感染药物的疗效受到了影响。因此,迫切需要寻找新的抗菌药物靶点和药物候选物来治疗 XDR 沙门氏菌。据观察,XDR H58 菌株的全基因组序列包含大量具有未知细胞和生物学功能的假设蛋白。因此,对这些蛋白进行功能和结构注释以鉴定新的药物靶点是必不可少的。

方法

在本研究中,应用比较基因组学和蛋白质组学方法,在比较伤寒沙门氏菌 MDR 和 NR 菌株的基础上,寻找 XDR 菌株中的新型药物靶点。

结果

通过确定其理化性质、亚细胞定位、功能注释和基于结构的研究,对大约 350 个假设蛋白进行了表征。结果,只有 5 个蛋白被优先选为必需、可药用和毒力蛋白。此外,只有一个蛋白即 WP_000916613.1 被高度置信地进行了功能注释,并进行了进一步的基于结构的分析。

结论

本研究提出了一个来自 XDR S. typhi 蛋白质组的假设蛋白作为潜在的药理学靶点,针对该靶点可以预测新型治疗候选物。本研究的结果可能会导致制定一套通用的流程,以更好地理解假设蛋白在沙门氏菌乃至其他病原体发病机制中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4420/8761513/493a3a7602de/10529_2021_3219_Fig1_HTML.jpg

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