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[细菌名称]及其他[细菌名称]属的必需基因指导新型药物和疫苗的研发。 (注:原文中两个[细菌名称]处需要根据实际所指细菌名称进行准确替换)

Essential Genes of and Other spp. Guide the Development of New Drugs and Vaccines.

作者信息

Bekaert Michaël, Goffin Nikki, McMillan Stuart, Desbois Andrew P

机构信息

Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, United Kingdom.

出版信息

Front Microbiol. 2021 Oct 20;12:755801. doi: 10.3389/fmicb.2021.755801. eCollection 2021.

Abstract

Essential genes in bacterial pathogens are potential drug targets and vaccine candidates because disrupting their function is lethal. The development of new antibiotics, in addition to effective prevention measures such as vaccination, contributes to addressing the global problem of bacterial antibiotic resistance. The aim of this present study was to determine the essential genes of , a bacterial pathogen of aquatic animals, as a means to identify putative targets for novel drugs and to assist the prioritisation of potential vaccine candidates. Essential genes were characterised by a Tn-seq approach using the TnSC189 mariner transposon to construct a library of 52,662 insertion mutants. In total, 329 essential genes were identified, with 34.7% found within the core genome of this species; each of these genes represents a strong potential drug target. Seven essential gene products were predicted to reside in the cell membrane or be released extracellularly, thus serving as putative vaccine candidates. Comparison to essential gene data from five other studies of species revealed 13 proteins to be conserved across the studies, while 25 genes were specific to and not found to be essential in the other spp. This study provides new information on the essential genes of species and the methodology may be applied to other pathogens to guide the development of new drugs and vaccines, which will assist efforts to counter antibiotic resistance.

摘要

细菌病原体中的必需基因是潜在的药物靶点和疫苗候选物,因为破坏它们的功能是致命的。除了有效的预防措施(如接种疫苗)外,开发新抗生素有助于解决全球细菌抗生素耐药性问题。本研究的目的是确定一种水生动物细菌病原体的必需基因,以此作为识别新型药物推定靶点并协助确定潜在疫苗候选物优先级的一种手段。通过使用TnSC189水手转座子的Tn-seq方法构建了一个包含52,662个插入突变体的文库,对必需基因进行了表征。总共鉴定出329个必需基因,其中34.7%位于该物种的核心基因组中;这些基因中的每一个都代表着强大的潜在药物靶点。预测有七种必需基因产物位于细胞膜中或释放到细胞外,因此可作为推定的疫苗候选物。与其他五项关于该物种的研究中的必需基因数据进行比较,发现有13种蛋白质在各项研究中是保守的,而有25个基因是该物种特有的,在其他物种中未发现是必需的。本研究提供了关于该物种必需基因的新信息,并且该方法可能适用于其他病原体,以指导新药和疫苗的开发,这将有助于对抗抗生素耐药性的努力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da5f/8564382/5625339d1e6d/fmicb-12-755801-g0001.jpg

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