Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave, Davis, CA 95616, USA.
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave, Davis, CA 95616, USA; Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus Givat-Ram, Jerusalem 9190401, Israel.
Cell Host Microbe. 2020 Dec 9;28(6):789-797.e5. doi: 10.1016/j.chom.2020.10.009.
The colonic microbiota exhibits cross-sectional heterogeneity, but the mechanisms that govern its spatial organization remain incompletely understood. Here we used Citrobacter rodentium, a pathogen that colonizes the colonic surface, to identify microbial traits that license growth and survival in this spatial niche. Previous work showed that during colonic crypt hyperplasia, type III secretion system (T3SS)-mediated intimate epithelial attachment provides C. rodentium with oxygen for aerobic respiration. However, we find that prior to the development of colonic crypt hyperplasia, T3SS-mediated intimate attachment is not required for aerobic respiration but for hydrogen peroxide (HO) respiration using cytochrome c peroxidase (Ccp). The epithelial NADPH oxidase NOX1 is the primary source of luminal HO early after C. rodentium infection and is required for Ccp-dependent growth. Our results suggest that NOX1-derived HO is a resource that governs bacterial growth and survival in close proximity to the mucosal surface during gut homeostasis.
结肠微生物群表现出横断面异质性，但控制其空间组织的机制仍不完全清楚。在这里，我们使用定植于结肠表面的病原体柠檬酸杆菌（Citrobacter rodentium）来鉴定在这个空间生态位中许可生长和存活的微生物特征。之前的工作表明，在结肠隐窝增生期间，III 型分泌系统（T3SS）介导的紧密上皮附着为柠檬酸杆菌提供了有氧呼吸所需的氧气。然而，我们发现，在结肠隐窝增生发展之前，T3SS 介导的紧密附着对于有氧呼吸不是必需的，而是对于使用细胞色素 c 过氧化物酶（Ccp）的过氧化氢（HO）呼吸是必需的。上皮 NADPH 氧化酶 NOX1 是柠檬酸杆菌感染后早期腔 HO 的主要来源，并且是 Ccp 依赖性生长所必需的。我们的结果表明，NOX1 衍生的 HO 是一种资源，在肠道稳态期间，它控制着靠近粘膜表面的细菌生长和存活。
