Regulated virulence controls the ability of a pathogen to compete with the gut microbiota
Open accessAbstract
The virulence mechanisms that allow pathogens to colonize the intestine remain unclear. Here, we show that germ-free animals are unable to eradicate Citrobacter rodentium, a model for human infections with attaching and effacing bacteria. Early in infection, virulence genes were expressed and required for pathogen growth in conventionally raised mice but not germ-free mice. Virulence gene expression was down-regulated during the late phase of infection, which led to relocation of the pathogen to the intestinal lumen where it was outcompeted by commensals. The ability of commensals to outcompete C. rodentium was determined, at least in part, by the capacity of the pathogen and commensals to grow on structurally similar carbohydrates. Thus, pathogen colonization is controlled by bacterial virulence and through competition with metabolically related commensals.
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When exposed to an intestinal pathogen, the barrier function of the intestinal microbiota depends on the stability of the bacterial community, its competitiveness in nutrient supply, and its ability to adapt to the new redox status of the mucosal environment.
“When exposed to an intestinal pathogen, the barrier function of the intestinal microbiota depends on the stability of the bacterial community, its competitiveness in nutrient supply, and its ability to adapt to the new redox status of the mucosal environment. 87”
From Key determinants of success in fecal microbiota transplantation: From microbiome to clinic (2023) · cites this paper as [87]
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- Authors
- Kamada, N., Kim, Y.-G., Sham, H. P., Vallance, B. A., Puente, J. L., Martens, E. C., & Núñez, G.
- Affiliations
- University of Michigan (US)
- University of British Columbia (CA)
- Universidad Nacional Autónoma de México (MX)
- Corresponding author
- Núñez, Gabriel
- ORCID
- Venue
- Science
- Published
- 2012-06-08
- Volume
- 336
- Issue
- 6086
- Pages
- 1325-1329
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3439148
- OpenAlex
- W1990473825
- Cited by
- 682
- References
- 23
- Citations by year
- 2026: 28 · 2025: 40 · 2024: 48 · 2023: 54 · 2022: 53 · 2021: 75 · 2020: 48 · 2019: 51 · 2018: 50 · 2017: 37 · 2016: 44 · 2015: 50 · 2014: 43 · 2013: 47 · 2012: 14
- FWCI
- 30.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Crohn's and Colitis Foundation
- Canadian Institutes of Health Research
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 61707, DK091191, R01DK095782, R01DK061707, R01DK091191)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Citrobacter rodentium, virulence gene regulation, gut microbiota, commensal bacteria, pathogen colonization, germ-free mice, carbohydrate metabolism, intestinal colonization, host-microbe interactions
- MeSH terms
- Animals, Bacterial Proteins, Bacteroides, Enterobacteriaceae Infections, Escherichia coli, Feces, Germ-Free Life, Intestinal Mucosa, Intestines, Mice, Inbred C57BL, Specific Pathogen-Free Organisms, Gene Expression Regulation, Bacterial, Virulence Factors, Citrobacter rodentium, Mice, Metagenome, Microbial Interactions, Bacterial Load
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