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.
Original language | American English |
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Pages (from-to) | 789-797.e5 |
Journal | Cell Host and Microbe |
Volume | 28 |
Issue number | 6 |
DOIs | |
State | Published - 9 Dec 2020 |
Bibliographical note
Funding Information:We would like to thank the UNC National Gnotobiotic Rodent Resource Center for kindly providing germ-free C57BL/6J mice. Y.L. was supported by Vaadia-BARD Postdoctoral Fellowship FI-505-2014. Work in A.J.B.’s lab was supported by USDA/NIFA award 2015-67015-22930 (A.J.B), Crohn's and Colitis Foundation of America Senior Investigator Award # 650976 and by Public Health Service Grants AI36309 (L.F.Z.), AI044170 (A.J.B.), AI096528 (A.J.B.), AI112445 (A.J.B.), AI146432 (A.J.B.) and AI112949 (A.J.B.). Conceptualization, B.M.M. and A.J.B. Methodology, B.M.M. L.F.Z. M.J.L. H.N. Y.L. K.K.J. E.M.S. C.R.T. B.P.B. and A.J.B.; Investigation, B.M.M. L.F.Z. M.J.L. H.N. Y.L. K.K.J. C.R.T. B.P.B. and A.J.B.; Resources, A.J.B. Funding Acquisition, Y.L. L.F.Z. and A.J.B.; Writing – Original Draft, B.M.M. and A.J.B.; Writing – Review & Editing, B.M.M. Y.L. K.K.J. B.P.B. and A.J.B.; Supervision, B.M.M. Y.L. and A.J.B. The authors declare no competing interests.
Funding Information:
We would like to thank the UNC National Gnotobiotic Rodent Resource Center for kindly providing germ-free C57BL/6J mice. Y.L. was supported by Vaadia-BARD Postdoctoral Fellowship FI-505-2014 . Work in A.J.B.’s lab was supported by USDA /NIFA award 2015-67015-22930 (A.J.B), Crohn’s and Colitis Foundation of America Senior Investigator Award # 650976 and by Public Health Service Grants AI36309 (L.F.Z.), AI044170 (A.J.B.), AI096528 (A.J.B.), AI112445 (A.J.B.), AI146432 (A.J.B.) and AI112949 (A.J.B.).
Publisher Copyright:
© 2020 Elsevier Inc.
Keywords
- Biogeography
- Citrobacter
- Habitat filters
- Mirobiota
- NADPH oxidase