A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection
A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection
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DOI：
10.1371/journal.pone.0067155
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发表时间：
2013-06-26
期刊：
影响因子：
3.7
通讯作者：
Adkins, Joshua N.
中科院分区：
文献类型：
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作者：
Kaiser, Brooke L. Deatherage;Li, Jie;Adkins, Joshua N.
宿主固有的微生物（“微生物组”或“微生物群”）通过影响宿主-病原体相互作用来改变感染结果的潜力在很大程度上是未知的。我们使用多组学“系统”方法，结合蛋白质组学、代谢组学、糖组学和宏基因组学，探索小鼠宿主、病原体肠道沙门氏菌鼠伤寒血清型（S.鼠伤寒沙门氏菌），和肠道微生物在肠道感染S。鼠伤寒。我们发现蛋白质组学证据表明，S。鼠伤寒杆菌在没有抗生素预处理的情况下在感染的129/SvJ小鼠肠道内茁壮成长，诱导炎症并破坏肠道微生物组（例如，例如，在一个实施例中，抑制拟杆菌门和厚壁菌门，同时促进沙门氏菌和肠球菌的生长）。宿主微生物群结构的改变与肠道环境变化高度相关，包括肠道微生物群通常消耗的代谢物的积累。最后，S.鼠伤寒的生命周期进行了调查，蛋白质组学和糖组学证据表明，S。鼠伤寒沙门氏菌可能利用增加的岩藻糖部分代谢岩藻糖，同时在肠道中生长。应用多组学测量沙门氏菌诱导的肠道炎症提供了深入了解宿主，病原体和微生物组之间的发病机制期间采用的复杂分子策略。
The potential for commensal microorganisms indigenous to a host (the 'microbiome' or 'microbiota') to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics "systems'' approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e. g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alteration of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium's lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.