Transcriptome and interactome-based analyses to unravel crucial proteins and pathways involved in Acinetobacter baumannii pathogenesis.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-11-15 DOI:10.1007/s11030-024-11041-1

Aishwarya Swain, Smruti Sikha Senapati, Archana Pan

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Abstract

The present study employed an integrated transcriptome and interactome-based analyses to identify key proteins and pathways associated with Acinetobacter baumannii infection towards the development of novel therapeutics against this pathogen. Transcriptome analysis of A.baumannii strains (ATCC 17978 and AbH12O-A2) identified 253 and 619 differentially expressed genes (DEGs), respectively. These genes were involved in essential molecular functions, including DNA binding, metal ion binding, and oxidoreductase activity. The centrality and module analyses of these identified DEGs had shortlisted 27 and 41 hub proteins, which were central to the ATCC 17978 and AbH12O-A2 networks, and essential for bacterial survival. Significantly, three proteins (SecA, glutathione synthase, and aromatic-amino-acid transaminase) from the ATCC 17978 strain and seven proteins (ATP synthase subunit alpha, translation initiation factor IF-2, SecY, elongation factors G, Tu, and Ts, and tRNA guanine-N1-methyltransferase) from the AbH12O-A2 strain showed interactions with human proteins, identified through host-pathogen interaction (HPI) analysis of hub proteins (referred as hub-HPI proteins). These proteins were observed to participate in vital pathways, including glutathione metabolism, secondary metabolite biosynthesis and quorum sensing. Targeting these hub-HPI proteins through novel therapeutic strategies holds the potential to disrupt the critical bacterial pathways, thereby controlling A. baumannii infections. Furthermore, their localization analysis indicated that nine proteins were cytoplasmic and one was membrane protein. Among them, six were druggable and four were novel proteins. Overall, this comprehensive study provides valuable insights into the crucial proteins and pathways involved during A. baumannii infection, and offers potential therapeutic targets for designing novel antimicrobial agents to tackle the pathogen.

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基于转录组和相互作用组的分析，揭示鲍曼不动杆菌致病过程中的关键蛋白和途径。

本研究采用了基于转录组和相互作用组的综合分析方法，以确定与鲍曼不动杆菌感染相关的关键蛋白和通路，从而开发出针对这种病原体的新型疗法。对鲍曼不动杆菌菌株（ATCC 17978 和 AbH12O-A2）的转录组分析分别发现了 253 个和 619 个差异表达基因（DEGs）。这些基因参与了重要的分子功能，包括 DNA 结合、金属离子结合和氧化还原酶活性。通过对这些已识别的 DEGs 进行中心性和模块分析，分别筛选出了 27 个和 41 个枢纽蛋白，它们是 ATCC 17978 和 AbH12O-A2 网络的核心，对细菌的生存至关重要。值得注意的是，ATCC 17978菌株的3个蛋白质（SecA、谷胱甘肽合酶和芳香族氨基酸转氨酶）和AbH12O-A2菌株的7个蛋白质（ATP合酶亚基α、翻译起始因子IF-2、SecY、延伸因子G、Tu和Ts以及tRNA鸟嘌呤-N1-甲基转移酶）显示出与人类蛋白质的相互作用。据观察，这些蛋白参与了重要的途径，包括谷胱甘肽代谢、次级代谢物生物合成和法定量感应。通过新型治疗策略靶向这些枢纽-HPI 蛋白，有可能破坏关键的细菌通路，从而控制鲍曼尼氏菌感染。此外，它们的定位分析表明，9 个蛋白是细胞质蛋白，1 个是膜蛋白。其中，6 个是药物蛋白，4 个是新型蛋白。总之，这项全面的研究为人们深入了解鲍曼不动杆菌感染过程中涉及的关键蛋白和途径提供了宝贵的信息，并为设计新型抗菌药物来对付这种病原体提供了潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;