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弯曲杆菌亚种:比较基因组学和潜在毒力靶标的预测。

Campylobacter fetus subspecies: comparative genomics and prediction of potential virulence targets.

机构信息

Federal University of Minas Gerais, Belo Horizonte, 31907-270, Minas Gerais, Brazil.

出版信息

Gene. 2012 Oct 25;508(2):145-56. doi: 10.1016/j.gene.2012.07.070. Epub 2012 Aug 6.

Abstract

The genus Campylobacter contains pathogens causing a wide range of diseases, targeting both humans and animals. Among them, the Campylobacter fetus subspecies fetus and venerealis deserve special attention, as they are the etiological agents of human bacterial gastroenteritis and bovine genital campylobacteriosis, respectively. We compare the whole genomes of both subspecies to get insights into genomic architecture, phylogenetic relationships, genome conservation and core virulence factors. Pan-genomic approach was applied to identify the core- and pan-genome for both C. fetus subspecies and members of the genus. The C. fetus subspecies conserved (76%) proteome were then analyzed for their subcellular localization and protein functions in biological processes. Furthermore, with pathogenomic strategies, unique candidate regions in the genomes and several potential core-virulence factors were identified. The potential candidate factors identified for attenuation and/or subunit vaccine development against C. fetus subspecies contain: nucleoside diphosphate kinase (Ndk), type IV secretion systems (T4SS), outer membrane proteins (OMP), substrate binding proteins CjaA and CjaC, surface array proteins, sap gene, and cytolethal distending toxin (CDT). Significantly, many of those genes were found in genomic regions with signals of horizontal gene transfer and, therefore, predicted as putative pathogenicity islands. We found CRISPR loci and dam genes in an island specific for C. fetus subsp. fetus, and T4SS and sap genes in an island specific for C. fetus subsp. venerealis. The genomic variations and potential core and unique virulence factors characterized in this study would lead to better insight into the species virulence and to more efficient use of the candidates for antibiotic, drug and vaccine development.

摘要

弯曲菌属包含引起广泛疾病的病原体, targeting both humans and animals. 其中,弯曲菌胎儿亚种胎儿和 venerealis 值得特别关注,因为它们分别是人类细菌性肠胃炎和牛生殖器弯曲菌病的病原体。我们比较了这两个亚种的全基因组,以深入了解基因组结构、系统发育关系、基因组保守性和核心毒力因子。泛基因组方法被应用于识别 C. fetus 亚种和属成员的核心和泛基因组。然后分析了 C. fetus 亚种保守(76%)的蛋白质组,以了解它们在亚细胞定位和生物过程中的蛋白质功能。此外,采用病原体基因组学策略,鉴定了基因组中独特的候选区域和几个潜在的核心毒力因子。针对 C. fetus 亚种的减毒和/或亚单位疫苗开发的潜在候选因素包括:核苷二磷酸激酶(Ndk)、IV 型分泌系统(T4SS)、外膜蛋白(OMP)、底物结合蛋白 CjaA 和 CjaC、表面排列蛋白、sap 基因和细胞致死扩张毒素(CDT)。重要的是,许多这些基因位于存在水平基因转移信号的基因组区域中,因此被预测为潜在的致病性岛。我们在特定于 C. fetus subsp. fetus 的一个岛上发现了 CRISPR 基因座和 dam 基因,在特定于 C. fetus subsp. venerealis 的一个岛上发现了 T4SS 和 sap 基因。本研究中所描述的基因组变异和潜在的核心和独特毒力因子将有助于更好地了解该物种的毒力,并更有效地利用候选抗生素、药物和疫苗开发。

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