Anaerobic Respiration of NOX1-Derived Hydrogen Peroxide Licenses Bacterial Growth at the Colonic Surface

Cell Host Microbe. 2020 Dec 9;28(6):789-797.e5. doi: 10.1016/j.chom.2020.10.009.

Abstract

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 (H2O2) respiration using cytochrome c peroxidase (Ccp). The epithelial NADPH oxidase NOX1 is the primary source of luminal H2O2 early after C. rodentium infection and is required for Ccp-dependent growth. Our results suggest that NOX1-derived H2O2 is a resource that governs bacterial growth and survival in close proximity to the mucosal surface during gut homeostasis.

Keywords: Biogeography; Citrobacter; Habitat filters; Mirobiota; NADPH oxidase.

MeSH terms

  • Anaerobiosis
  • Animals
  • Citrobacter rodentium / growth & development*
  • Citrobacter rodentium / metabolism*
  • Colon / microbiology
  • Cytochrome-c Peroxidase / physiology*
  • DNA, Bacterial
  • Feces / microbiology
  • Female
  • Germ-Free Life
  • Homeostasis
  • Host-Pathogen Interactions
  • Hydrogen Peroxide / metabolism*
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidase 1 / physiology*
  • RNA, Ribosomal, 16S
  • Specific Pathogen-Free Organisms
  • Type III Secretion Systems / physiology

Substances

  • DNA, Bacterial
  • RNA, Ribosomal, 16S
  • Type III Secretion Systems
  • Hydrogen Peroxide
  • Cytochrome-c Peroxidase
  • NADPH Oxidase 1
  • NOX1 protein, mouse