泛耐药性普罗维登西亚菌株 MRSN845308 假想蛋白质的鉴定和功能注释,以设计抗菌药物靶标。

IF 2.3 Q3 BIOCHEMICAL RESEARCH METHODS
Bioinformatics and Biology Insights Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI:10.1177/11779322241280580
Dipta Chandra Pal, Tasnimul Arabi Anik, Atiq Abrar Rahman, S M Mahfujur Rahman
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引用次数: 0

摘要

普罗维登菌(Providencia rettgeri)越来越多地引发多种感染,包括尿路感染、烧伤后伤口感染、新生儿败血症等。伴随着固有和获得性抗生素耐药性,耐药性 P rettgeri 分离物的出现加剧了治疗此类感染的挑战,因此有必要开发新型疗法。假想蛋白(HPs)构成了细胞蛋白的主要部分,可以成为这些新型疗法的靶标。本研究对一株泛耐药(PDR)P rettgeri 菌株(MRSN845308)的 410 个假想蛋白进行了功能注释,并从理化性质、定位、毒力、本质、可药性和功能性等方面对其进行了表征。在 410 个 HPs 中,VirulentPred 2.0 工具和 VICMpred 共预测出 33 个 HPs 具有毒力,而根据 STRING v12 数据库,48 个 HPs 是高度互作蛋白。BlastKOALA 和 eggNOG-mapper v2.1.12 预测有 13 个 HPs 涉及核黄素代谢和脂多糖生物合成等多个代谢途径。总体而言,有 83 个 HPs 被选为主要药物靶点;但是,经过非同源搜索和本质分析后,只剩下 80 个 HPs。此外,根据 DrugBank 5.1.12,所有 HPs 都被检测为新的药物靶点。考虑到膜蛋白和细胞外蛋白的潜力,根据 PSORTb v3.0.3、CELLO v.2.5、BUSCA、SOSUIGramN 和 PSLpred 的综合预测,选出了 29 个 HPs(细胞外膜、外膜和内膜)。根据这些 HPs 在美国国家生物技术信息中心同源蛋白质组(NCBI-IPG)中不同菌株 P rettgeri 序列中的普遍性,选出 5 个 HPs 作为最终药物靶标。此外,还有 5 个注释为转运蛋白的 HPs 也被添加到了列表中。由于我们的靶标没有晶体结构,因此由 AlphaFold 3 支持的 AlphaFold 服务器对所选 HPs 的三维结构进行了预测。我们的发现可能有助于更好地理解病毒的毒性和致病机制,而最新的注释可以使未表征的 HPs 更容易被确定为新型疗法的靶标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification and Functional Annotation of Hypothetical Proteins of Pan-Drug-Resistant Providencia rettgeri Strain MRSN845308 Toward Designing Antimicrobial Drug Targets.

Providencia rettgeri has increasingly been responsible for several infections, including urinary tract, post-burn wounds, neonatal sepsis, and others. The emergence of drug-resistant isolates of P rettgeri, accompanied by intrinsic and acquired antibiotic resistance, has exacerbated the challenge of treating such infections, necessitating the development of novel therapeutics. Hypothetical proteins (HPs) form a major portion of cellular proteins and can be targeted by these novel therapeutics. In this study, 410 HPs from a pan-drug-resistant (PDR) P rettgeri strain (MRSN845308) were functionally annotated and characterized by physicochemical properties, localization, virulence, essentiality, druggability, and functionality. Among 410 HPs, the VirulentPred 2.0 tool and VICMpred combinedly predicted 33 HPs as virulent, whereas 48 HPs were highly interacting proteins based on the STRING v12 database. BlastKOALA and eggNOG-mapper v2.1.12 predicted 13 HPs involved in several metabolic pathways like Riboflavin metabolism and Lipopolysaccharide biosynthesis. Overall, 83 HPs were selected as primary drug targets; however, only 80 remained after nonhomology searching and essentiality analysis. In addition, all were detected as novel drug targets according to DrugBank 5.1.12. Considering the potential of membrane and extracellular proteins, 29 HPs (extracellular, outer, and inner membrane) were selected based on the combined prediction from PSORTb v3.0.3, CELLO v.2.5, BUSCA, SOSUIGramN, and PSLpred. According to the prevalence of those HPs in different strains of P rettgeri sequences in National Center for Biotechnology Information Identical Protein Groups (NCBI-IPG), 5 HPs were selected as final drug targets. In addition, 5 other HPs annotated as transporter proteins were also added to the list. As no crystal structures of our targets are present, 3-dimensional structures of selected HPs were predicted by the AlphaFold Server powered by AlphaFold 3. Our findings might facilitate a better understanding of the mechanism of virulence and pathogenesis, and up-to-date annotations can make uncharacterized HPs easy to identify as targets for novel therapeutics.

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来源期刊
Bioinformatics and Biology Insights
Bioinformatics and Biology Insights BIOCHEMICAL RESEARCH METHODS-
CiteScore
6.80
自引率
1.70%
发文量
36
审稿时长
8 weeks
期刊介绍: Bioinformatics and Biology Insights is an open access, peer-reviewed journal that considers articles on bioinformatics methods and their applications which must pertain to biological insights. All papers should be easily amenable to biologists and as such help bridge the gap between theories and applications.
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