Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Host Microbe. 2023 Mar 8;31(3):405-417.e5. doi: 10.1016/j.chom.2023.01.017. Epub 2023 Feb 21.
The molecular understanding of host-pathogen interactions in the gastrointestinal (GI) tract of superspreader hosts is incomplete. In a mouse model of chronic, asymptomatic Salmonella enterica serovar Typhimurium (S. Tm) infection, we performed untargeted metabolomics on the feces of mice and found that superspreader hosts possess distinct metabolic signatures compared with non-superspreaders, including differential levels of L-arabinose. RNA-seq on S. Tm from superspreader fecal samples showed increased expression of the L-arabinose catabolism pathway in vivo. By combining bacterial genetics and diet manipulation, we demonstrate that diet-derived L-arabinose provides S. Tm a competitive advantage in the GI tract, and expansion of S. Tm in the GI tract requires an alpha-N-arabinofuranosidase that liberates L-arabinose from dietary polysaccharides. Ultimately, our work shows that pathogen-liberated L-arabinose from the diet provides a competitive advantage to S. Tm in vivo. These findings propose L-arabinose as a critical driver of S. Tm expansion in the GI tracts of superspreader hosts.
在超级传播宿主的胃肠道（GI）中，宿主-病原体相互作用的分子理解还不完全。在慢性、无症状鼠伤寒沙门氏菌（S. Tm）感染的小鼠模型中，我们对小鼠粪便进行了非靶向代谢组学分析，发现超级传播宿主与非超级传播宿主具有明显不同的代谢特征，包括 L-阿拉伯糖的差异水平。对超级传播者粪便中 S. Tm 的 RNA-seq 显示，L-阿拉伯糖分解代谢途径的表达在体内增加。通过结合细菌遗传学和饮食操作，我们证明饮食来源的 L-阿拉伯糖为 S. Tm 在胃肠道中提供了竞争优势，而 S. Tm 在胃肠道中的扩张需要一种 alpha-N-阿拉伯呋喃糖苷酶，该酶从膳食多糖中释放 L-阿拉伯糖。最终，我们的工作表明，饮食中病原体释放的 L-阿拉伯糖为 S. Tm 在体内的扩张提供了竞争优势。这些发现表明 L-阿拉伯糖是超级传播宿主胃肠道中 S. Tm 扩张的关键驱动因素。
