Comparative genomics analysis to differentiate metabolic and virulence gene potential in gastric versus enterohepatic Helicobacter species.
Comparative genomics analysis to differentiate metabolic and virulence gene potential in gastric versus enterohepatic Helicobacter species.
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DOI：
10.1186/s12864-018-5171-2
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发表时间：
2018-11-20
期刊：
影响因子：
4.4
通讯作者：
Fox JG
中科院分区：
文献类型：
--
作者：
Mannion A;Shen Z;Fox JG
幽门螺杆菌属是与胃肠道炎症相关的革兰氏阴性、微氧、鞭毛、黏液细菌，根据宿主种类和定植生态位分为胃或肠肝幽门螺杆菌种（EHS）。虽然有超过30个官方物种，但由于它们栖息于不同的宿主和定植生态位，人们对EHS的生理和致病机制知之甚少，以及胃与EHS的遗传因素差异。本研究的目的是对100多个胃和EHS基因组进行全属比较分析，以确定区分这些幽门螺杆菌物种的遗传决定因素，并提供有关它们对不同宿主、定植生态位和毒力机制的进化/适应的见解。全基因组系统发育根据其假定的胃或EHS分类组织幽门螺杆菌物种。同源物分析显示胃和EHS基因组在生理和毒力相关基因上存在很大的异质性。代谢重建预测，与胃的物种不同，EHS表现为糖水解，依赖于氨基酸/有机酸来促进代谢。此外，胃物种缺乏在EHS中发现的几种氨基酸和嘌呤的新生生物合成途径，而是依赖于环境摄取/回收途径。胃和EHS基因组之间的毒力因子基因比较发现重叠但不同的谱，包括典型的细胞毒素、外膜蛋白、分泌系统和生存因子。预测代谢功能的主要差异表明，胃物种和EHS可能分别是为了在营养丰富的胃和营养缺乏的环境中生存而进化的。毒力因子基因谱的对比表明，胃种和EHS可能利用不同的致病机制慢性感染宿主，引起炎症和组织损伤。本研究的发现为胃和EHS的遗传差异提供了新的见解，并支持了未来实验研究表征这些病原体的必要性。本文的在线版本（10.1186/s12864-018-5171-2）包含补充材料，授权用户可使用。
The genus Helicobacter are gram-negative, microaerobic, flagellated, mucus-inhabiting bacteria associated with gastrointestinal inflammation and classified as gastric or enterohepatic Helicobacter species (EHS) according to host species and colonization niche. While there are over 30 official species, little is known about the physiology and pathogenic mechanisms of EHS, which account for most in the genus, as well as what genetic factors differentiate gastric versus EHS, given they inhabit different hosts and colonization niches. The objective of this study was to perform a whole-genus comparative analysis of over 100 gastric versus EHS genomes in order to identify genetic determinants that distinguish these Helicobacter species and provide insights about their evolution/adaptation to different hosts, colonization niches, and mechanisms of virulence. Whole-genome phylogeny organized Helicobacter species according to their presumed gastric or EHS classification. Analysis of orthologs revealed substantial heterogeneity in physiological and virulence-related genes between gastric and EHS genomes. Metabolic reconstruction predicted that unlike gastric species, EHS appear asaccharolytic and dependent on amino/organic acids to fuel metabolism. Additionally, gastric species lack de novo biosynthetic pathways for several amino acids and purines found in EHS and instead rely on environmental uptake/salvage pathways. Comparison of virulence factor genes between gastric and EHS genomes identified overlapping yet distinct profiles and included canonical cytotoxins, outer membrane proteins, secretion systems, and survival factors. The major differences in predicted metabolic function suggest gastric species and EHS may have evolved for survival in the nutrient-rich stomach versus the nutrient-devoid environments, respectively. Contrasting virulence factor gene profiles indicate gastric species and EHS may utilize different pathogenic mechanisms to chronically infect hosts and cause inflammation and tissue damage. The findings from this study provide new insights into the genetic differences underlying gastric versus EHS and support the need for future experimental studies to characterize these pathogens. The online version of this article (10.1186/s12864-018-5171-2) contains supplementary material, which is available to authorized users.
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