Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nat Chem Biol. 2021 Nov;17(11):1199-1208. doi: 10.1038/s41589-021-00894-4. Epub 2021 Oct 21.
The microbial cell surface is a site of critical microbe-host interactions that often control infection outcomes. Defining the set of host proteins present at this interface has been challenging. Here we used a surface-biotinylation approach coupled to quantitative mass spectrometry to identify and quantify both bacterial and host proteins present on the surface of diarrheal fluid-derived Vibrio cholerae in an infant rabbit model of cholera. The V. cholerae surface was coated with numerous host proteins, whose abundance were driven by the presence of cholera toxin, including the C-type lectin SP-D. Mice lacking SP-D had enhanced V. cholerae intestinal colonization, and SP-D production shaped both host and pathogen transcriptomes. Additional host proteins (AnxA1, LPO and ZAG) that bound V. cholerae were also found to recognize distinct taxa of the murine intestinal microbiota, suggesting that these host factors may play roles in intestinal homeostasis in addition to host defense.
微生物细胞表面是微生物-宿主相互作用的关键部位，通常控制着感染的结果。定义存在于该界面的一组宿主蛋白一直具有挑战性。在这里，我们使用表面生物素化方法结合定量质谱法，在霍乱弧菌婴儿兔模型中鉴定和定量了腹泻液来源霍乱弧菌表面存在的细菌和宿主蛋白。霍乱弧菌表面覆盖着许多宿主蛋白，其丰度受霍乱毒素的存在所驱动，包括 C 型凝集素 SP-D。缺乏 SP-D 的小鼠具有增强的霍乱弧菌肠道定植，SP-D 的产生塑造了宿主和病原体的转录组。还发现与霍乱弧菌结合的其他宿主蛋白（AnxA1、LPO 和 ZAG）也能识别小鼠肠道微生物群的不同分类群，这表明这些宿主因子除了宿主防御外，还可能在肠道稳态中发挥作用。
