Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration

Lopez, Christopher A.; Miller, Brittany M.; Rivera-Chávez, Fabian; Velazquez, Eric M.; Byndloss, Mariana X.; Chávez-Arroyo, Alfredo; Lokken, Kristen L.; Tsolis, Renée M.; Winter, Sebastian E.; Bäumler, Andreas J.

doi:10.1126/science.aag3042

Cited by 201Escherichia coli research studiesGut microbiota and healthSalmonella and Campylobacter epidemiology

Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration

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Lopez, Christopher A., Miller, Brittany M., Rivera-Chávez, Fabian, Velazquez, Eric M., Byndloss, Mariana X., Chávez-Arroyo, Alfredo, Lokken, Kristen L., Tsolis, Renée M. +2 more·2016·Science

DOI 10.1126/science.aag3042PMC PMC5127919

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Abstract

Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C. rodentium infection. We conclude that C. rodentium uses its T3SS to induce histopathological lesions that generate an intestinal microenvironment in which growth of the pathogen is fueled by aerobic respiration.

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Molybdenum, as part of the molybdenum cofactor with pterin, is required for reductases and dehydrogenases in bacterial respiration that are important during Enterobacteriaceae infection.
“Molybdenum, when complexed with a pterin molecule to form a molybdenum cofactor, is necessary for the catalytic activity of reductases and dehydrogenases in bacterial respiration that are critical during infection by the Enterobacteriaceae (Lopez et al., 2016).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Lopez et al., 2016

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Authors: Lopez, C. A., Miller, B. M., Rivera-Chávez, F., Velazquez, E. M., Byndloss, M. X., Chávez-Arroyo, A., Lokken, K. L., Tsolis, R. M., Winter, S. E., & Bäumler, A. J.
Affiliations: University of California, Davis (US)
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
The University of Texas Southwestern Medical Center (US)
Corresponding author: Bäumler, Andreas J.
ORCID: Lopez, Christopher A.
Miller, Brittany M.
Rivera-Chávez, Fabian
Velazquez, Eric M.
Byndloss, Mariana X.
Lokken, Kristen L.
Tsolis, Renée M.
Winter, Sebastian E.
Bäumler, Andreas J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2016-09-16
Volume: 353
Issue: 6305
Pages: 1249-1253
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aag3042
PMC: PMC5127919
OpenAlex: W2519607762
Cited by: 201
References: 53
Citations by year: 2026: 15 · 2025: 19 · 2024: 15 · 2023: 22 · 2022: 19 · 2021: 27 · 2020: 19 · 2019: 24 · 2018: 21 · 2017: 14 · 2016: 5 · 2012: 1
FWCI: 20.54
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 365 d)
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: Public Health Service (AI044170, AI096528, AI107393, AI112949, AI098078, AI103248, AI112241, OD010931)
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 › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
Keywords: Citrobacter rodentium, type III secretion system, virulence factors, aerobic respiration, intestinal epithelial cell proliferation, Ki-67, Notch signaling, gamma-secretase inhibitors, dibenzazepine, host-pathogen interaction, intestinal oxygenation
MeSH terms: Aerobiosis, Animals, Colitis, Colon, Cytochromes, Dibenzazepines, Enterobacteriaceae Infections, Hyperplasia, Intestinal Mucosa, Mice, Inbred C3H, Mice, Inbred C57BL, Nitrates, Oxidoreductases, Gene Deletion, Ki-67 Antigen, Virulence Factors, Citrobacter rodentium, Electron Transport Chain Complex Proteins, Mice, Receptors, Notch, Amyloid Precursor Protein Secretases

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Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration

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