Clostridium scindens ATCC 35704: Integration of Nutritional Requirements, the Complete Genome Sequence, and Global Transcriptional Responses to Bile Acids
Clostridium scindens ATCC 35704: Integration of Nutritional Requirements, the Complete Genome Sequence, and Global Transcriptional Responses to Bile Acids
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DOI：
10.1128/aem.00052-19
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发表时间：
2019-04-01
影响因子：
4.4
通讯作者：
Ridlon, Jason M.
中科院分区：
文献类型：
--
作者：
Devendran, Saravanan;Shrestha, Rachana;Ridlon, Jason M.
在人类肠道中，梭菌ATCC 35704是一种优势细菌，也是主要的胆汁酸7 α-脱羟基厌氧菌之一。虽然这种生物体相对于胆汁酸代谢进行了充分的研究，但对C的基本营养和生理学知之甚少。白藓ATCC 35704。目的：测定C.除此之外，使用留一法（一种氨基酸组或维生素）来消除非必需氨基酸和维生素。通过这种方法，发现氨基酸色氨酸和三种维生素（核黄素、泛酸和吡哆醛）是C.你好在新开发的确定培养基中，C.葡萄糖发酵主要产生乙醇、乙酸盐、甲酸盐和H-2。C.通过PacBio测序完成了对ATCC 35704菌株的测序。在确定的培养条件下，结合转录组测序（RNA-Seq）的基因组序列的途径分析显示与生长要求和葡萄糖代谢的终产物一致。胆汁酸诱导显示复杂和差异的反应，胆酸和脱氧胆酸，包括潜在的新的胆汁酸诱导的基因参与胆酸代谢的表达。对毒性脱氧胆酸的反应包括预测参与DNA修复、氧化应激、细胞壁维持/代谢、伴侣蛋白合成和三分之一基因组下调的基因的表达。这些分析为C.这可能是重要的，在治疗疾病与增加结肠次级胆汁酸。肠杆菌是少数鉴定的能够将宿主胆酸转化为疾病相关的次级胆汁酸如脱氧胆酸的肠道细菌菌种之一。目前的工作代表了一个重要的进展，在了解营养需求和响应胆汁酸的医学重要的人类肠道细菌，C。白藓ATCC 35704。已经开发了一种成分确定的培养基，其将进一步理解在脊椎动物肠道中生长底物、辅因子和其他代谢物的背景下胆汁酸代谢。对完整基因组的分析支持这里报告的营养需求。在胆酸和脱氧胆酸存在的情况下，基因表达的全基因组转录组学分析提供了对C.将ATCC 35704转化为初级和次级胆汁酸。还揭示了在胆汁酸转运和代谢中具有功能潜力的基因。
In the human gut, Clostridium scindens ATCC 35704 is a predominant bacterium and one of the major bile acid 7 alpha-dehydroxylating anaerobes. While this organism is well-studied relative to bile acid metabolism, little is known about the basic nutrition and physiology of C. scindens ATCC 35704. To determine the amino acid and vitamin requirements of C. scindens, the leave-one-out (one amino acid group or vitamin) technique was used to eliminate the nonessential amino acids and vitamins. With this approach, the amino acid tryptophan and three vitamins (riboflavin, pantothenate, and pyridoxal) were found to be required for the growth of C. scindens. In the newly developed defined medium, C. scindens fermented glucose mainly to ethanol, acetate, formate, and H-2. The genome of C. scindens ATCC 35704 was completed through PacBio sequencing. Pathway analysis of the genome sequence coupled with transcriptome sequencing (RNA-Seq) under defined culture conditions revealed consistency with the growth requirements and end products of glucose metabolism. Induction with bile acids revealed complex and differential responses to cholic acid and deoxycholic acid, including the expression of potentially novel bile acid-inducible genes involved in cholic acid metabolism. Responses to toxic deoxycholic acid included expression of genes predicted to be involved in DNA repair, oxidative stress, cell wall maintenance/metabolism, chaperone synthesis, and downregulation of one-third of the genome. These analyses provide valuable insight into the overall biology of C. scindens which may be important in treatment of disease associated with increased colonic secondary bile acids.IMPORTANCE C. scindens is one of a few identified gut bacterial species capable of converting host cholic acid into disease associated secondary bile acids such as deoxycholic acid. The current work represents an important advance in understanding the nutritional requirements and response to bile acids of the medically important human gut bacterium, C. scindens ATCC 35704. A defined medium has been developed which will further the understanding of bile acid metabolism in the context of growth substrates, cofactors, and other metabolites in the vertebrate gut. Analysis of the complete genome supports the nutritional requirements reported here. Genome-wide transcriptomic analysis of gene expression in the presence of cholic acid and de oxycholic acid provides a unique insight into the complex response of C. scindens ATCC 35704 to primary and secondary bile acids. Also revealed are genes with the potential to function in bile acid transport and metabolism.