Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut.
Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut.
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DOI：
10.1128/mbio.00929-14
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发表时间：
2014-03-18
期刊：
影响因子：
6.4
通讯作者：
Bäumler AJ
中科院分区：
文献类型：
--
作者：
Nuccio SP;Bäumler AJ
沙门氏菌属包括一组与从胃肠炎到伤寒的疾病相关的病原体。我们对相对重新注释的沙门氏菌基因组进行了计算机分析，以确定指示疾病潜力的基因组特征。通过消除许多注释不一致和不准确的地方，重新注释的过程确定了一个由469个参与中枢厌氧代谢的基因组成的网络，这些基因在胃肠道病原体的基因组中是完整的，但在肠外病原体的基因组中会降解。这个大网络包含使胃肠道病原体能够利用炎症来源的营养物质以及用于沙门氏菌血清型富集和生化鉴别的许多生化反应的途径。因此，比较基因组分析确定了一个代谢网络，提供了营养物质的获取和利用的战略，是胃肠道病原体的特点的线索。虽然一些沙门氏菌血清型引起的感染仍然局限于肠道，但其他沙门氏菌血清型则传播到全身。在这里，我们比较了沙门氏菌的基因组，以确定区分胃肠道和肠外病原体的特征。我们确定了一个大的代谢网络，在胃肠道病原体中起作用，但在肠外病原体中衰减。虽然分类学家已经使用了几十年的经验，从这个网络的沙门氏菌血清型的富集和生化歧视的特点，我们的研究结果表明，这是一个“商业计划”的一部分，在发炎的胃肠道的增长。通过识别与胃肠炎相关的沙门氏菌血清型的大型代谢网络特征，我们的计算机分析为利用炎症来源的营养物质和淘汰竞争性肠道微生物的潜在策略提供了蓝图。
The Salmonella genus comprises a group of pathogens associated with illnesses ranging from gastroenteritis to typhoid fever. We performed an in silico analysis of comparatively reannotated Salmonella genomes to identify genomic signatures indicative of disease potential. By removing numerous annotation inconsistencies and inaccuracies, the process of reannotation identified a network of 469 genes involved in central anaerobic metabolism, which was intact in genomes of gastrointestinal pathogens but degrading in genomes of extraintestinal pathogens. This large network contained pathways that enable gastrointestinal pathogens to utilize inflammation-derived nutrients as well as many of the biochemical reactions used for the enrichment and biochemical discrimination of Salmonella serovars. Thus, comparative genome analysis identifies a metabolic network that provides clues about the strategies for nutrient acquisition and utilization that are characteristic of gastrointestinal pathogens. While some Salmonella serovars cause infections that remain localized to the gut, others disseminate throughout the body. Here, we compared Salmonella genomes to identify characteristics that distinguish gastrointestinal from extraintestinal pathogens. We identified a large metabolic network that is functional in gastrointestinal pathogens but decaying in extraintestinal pathogens. While taxonomists have used traits from this network empirically for many decades for the enrichment and biochemical discrimination of Salmonella serovars, our findings suggest that it is part of a “business plan” for growth in the inflamed gastrointestinal tract. By identifying a large metabolic network characteristic of Salmonella serovars associated with gastroenteritis, our in silico analysis provides a blueprint for potential strategies to utilize inflammation-derived nutrients and edge out competing gut microbes.