Salmonella enterica serovar Typhimurium is a pervasive enteric pathogen and ongoing global threat to public health. Ecological studies in the Salmonella impacted gut remain underrepresented in the literature, discounting microbiome mediated interactions that may inform Salmonella physiology during colonization and infection. To understand the microbial ecology of Salmonella remodeling of the gut microbiome, we performed multi-omics on fecal microbial communities from untreated and Salmonella-infected mice. Reconstructed genomes recruited metatranscriptomic and metabolomic data providing a strain-resolved view of the expressed metabolisms of the microbiome during Salmonella infection. These data informed possible Salmonella interactions with members of the gut microbiome that were previously uncharacterized. Salmonella-induced inflammation significantly reduced the diversity of genomes that recruited transcripts in the gut microbiome, yet increased transcript mapping was observed for seven members, among which Luxibacter and Ligilactobacillus transcript read recruitment was most prevalent. Metatranscriptomic insights from Salmonella and other persistent taxa in the inflamed microbiome further expounded the necessity for oxidative tolerance mechanisms to endure the host inflammatory responses to infection. In the inflamed gut lactate was a key metabolite, with microbiota production and consumption reported amongst members with detected transcript recruitment. We also showed that organic sulfur sources could be converted by gut microbiota to yield inorganic sulfur pools that become oxidized in the inflamed gut, resulting in thiosulfate and tetrathionate that support Salmonella respiration. This research advances physiological microbiome insights beyond prior amplicon-based approaches, with the transcriptionally active organismal and metabolic pathways outlined here offering intriguing intervention targets in the Salmonella-infected intestine.

中文翻译：

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肠道微生物群碳和硫代谢支持沙门氏菌感染


鼠伤寒沙门氏菌血清型是一种普遍的肠道病原体，对公共卫生构成持续的全球威胁。沙门氏菌影响肠道的生态学研究在文献中仍然代表性不足，忽视了微生物组介导的相互作用，这些相互作用可能在定植和感染期间为沙门氏菌生理学提供信息。为了了解肠道微生物组沙门氏菌重塑的微生物生态学，我们对未经治疗和沙门氏菌感染小鼠的粪便微生物群落进行了多组学研究。重建基因组招募了元转录组学和代谢组学数据，提供了沙门氏菌感染期间微生物组表达代谢的菌株分辨视图。这些数据表明了沙门氏菌与肠道微生物组成员之间可能存在的相互作用，而这些相互作用以前未被表征。沙门氏菌诱导的炎症显著降低了在肠道微生物组中募集转录本的基因组多样性，但观察到 7 个成员的转录本映射增加，其中 Luxibacter 和 Ligilactobacillus 转录本读长募集最为普遍。来自发炎微生物组中沙门氏菌和其他持久性分类群的元转录组学见解进一步阐明了氧化耐受机制承受宿主对感染的炎症反应的必要性。在发炎的肠道中，乳酸是一种关键的代谢物，在检测到转录本募集的成员中报告了微生物群的产生和消耗。我们还表明，有机硫源可以被肠道微生物群转化为无机硫库，这些硫库在发炎的肠道中被氧化，从而产生支持沙门氏菌呼吸的硫代硫酸盐和连四硫酸盐。 这项研究超越了以前基于扩增子的方法，推进了生理微生物组的见解，此处概述的转录活性有机体和代谢途径在沙门氏菌感染的肠道中提供了有趣的干预靶点。