Salmonella Typhimurium screen identifies shifts in mixed-acid fermentation during gut colonization

IF 20.6 1区 医学 Q1 MICROBIOLOGY
Bidong D. Nguyen, Anna Sintsova, Christopher Schubert, Andreas Sichert, Clio Scheidegger, Jana Näf, Julien Huttman, Verena Lentsch, Tim Keys, Christoph Rutschmann, Philipp Christen, Patrick Kiefer, Philipp Keller, Manja Barthel, Miguelangel Cuenca, Beat Christen, Uwe Sauer, Emma Slack, Julia A. Vorholt, Shinichi Sunagawa, Wolf-Dietrich Hardt
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Abstract

How enteric pathogens adapt their metabolism to a dynamic gut environment is not yet fully understood. To investigate how Salmonella enterica Typhimurium (S.Tm) colonizes the gut, we conducted an in vivo transposon mutagenesis screen in a gnotobiotic mouse model. Our data implicate mixed-acid fermentation in efficient gut-luminal growth and energy conservation throughout infection. During initial growth, the pathogen utilizes acetate fermentation and fumarate respiration. After the onset of gut inflammation, hexoses appear to become limiting, as indicated by carbohydrate analytics and the increased need for gluconeogenesis. In response, S.Tm adapts by ramping up ethanol fermentation for redox balancing and supplying the TCA cycle with α-ketoglutarate for additional energy. Our findings illustrate how S.Tm flexibly adapts mixed fermentation and its use of the TCA cycle to thrive in the changing gut environment. Similar metabolic wiring in other pathogenic Enterobacteriaceae may suggest a broadly conserved mechanism for gut colonization.

Abstract Image

伤寒沙门氏菌筛选确定肠道定植过程中混合酸发酵的变化
肠道病原体如何使其新陈代谢适应动态的肠道环境尚未完全清楚。为了研究伤寒沙门氏菌(S.Tm)如何在肠道内定植,我们在无饥饿感小鼠模型中进行了体内转座子诱变筛选。我们的数据表明,混合酸发酵参与了整个感染过程中肠道菌腔的高效生长和能量守恒。在生长初期,病原体利用醋酸发酵和富马酸呼吸。肠道炎症发生后,己糖似乎成为限制性物质,碳水化合物分析和葡萄糖生成需求的增加都表明了这一点。作为回应,S.Tm 通过加强乙醇发酵以实现氧化还原平衡,并向α-酮戊二酸 TCA 循环提供额外能量来进行适应。我们的研究结果说明了 S.Tm 是如何灵活地适应混合发酵并利用 TCA 循环在不断变化的肠道环境中茁壮成长的。其他致病性肠杆菌科细菌也有类似的代谢线路,这可能表明肠道定植有一个广泛保守的机制。
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来源期刊
Cell host & microbe
Cell host & microbe 生物-微生物学
CiteScore
45.10
自引率
1.70%
发文量
201
审稿时长
4-8 weeks
期刊介绍: Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.
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