QseC inhibition as an antivirulence approach for colitis-associated bacteria
Open accessAbstract
IBD mouse model revealed microbial features that discriminate between health and disease states. Enterobacteriaceae expansion and increased gene abundances for benzoate degradation, two-component systems, and bacterial motility proteins pointed to the potential involvement of a catecholamine-mediated bacterial signaling axis in colitis pathogenesis. Enterobacteriaceae sense and respond to microbiota-generated signals and host-derived catecholamines through the two-component quorum-sensing Escherichia coli regulators B and C (QseBC) system. On signal detection, QseC activates a cascade to induce virulence gene expression. Although a single pathogen has not been identified as a causative agent in IBD, adherent-invasive Escherichia coli (AIEC) have been implicated. Flagellar expression is necessary for the IBD-associated AIEC strain LF82 to establish colonization. Thus, we hypothesized that qseC inactivation could reduce LF82's virulence, and found that an absence of qseC leads to down-regulated flagellar expression and motility in vitro and reduced colonization in vivo. We extend these findings on the potential of QseC-based IBD therapeutics to three preclinical IBD models, wherein we observe that QseC blockade can effectively modulate colitogenic microbiotas to reduce intestinal inflammation. Collectively, our data support a role for QseC-mediated bacterial signaling in IBD pathogenesis and indicate that QseC inhibition may be a useful microbiota-targeted approach for disease management.
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Genetic inactivation of quorum-sensing Escherichia coli regulator C (QseC) can reduce the virulence and colonization capacity in a pathogenic, IBD-associated E. coli strain.
“Rooks et al. demonstrated that genetic inactivation of quorum-sensing Escherichia coli regulator C (QseC) can reduce the virulence and colonization capacity in a pathogenic, IBD-associated E. coli strain.”
From Stress triggers flare of inflammatory bowel disease in children and adults (2019) · cites this paper as [149]
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Research works printed but not linked: 1
- Mukhopadhya I, Hansen R, El-Omar EM, Hold GL (2012) IBD: What roles do Proteo- bacteria play? Nat Rev Gastroenterol Hepatol 9(4):219-230.
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Self-citation
- Authors
- Rooks, M. G., Veiga, P., Reeves, A. Z., Lavoie, S., Yasuda, K., Asano, Y., Yoshihara, K., Michaud, M., Wardwell-Scott, L., Gallini, C. A., Glickman, J. N., Sudo, N., Huttenhower, C., Lesser, C. F., & Garrett, W. S.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- Kyushu University (JP)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Garrett, Wendy S.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-12-15
- Volume
- 114
- Issue
- 1
- Pages
- 142-147
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5224399
- OpenAlex
- W2566319404
- Cited by
- 57
- References
- 58
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 5 · 2020: 8 · 2019: 8 · 2018: 1 · 2017: 9
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Cancer Institute (R01 CA154426)
- HHS | NIH | National Institute of General Medical Sciences (R01 GM099531)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- QseC, anti-virulence therapy, inflammatory bowel disease, adherent-invasive Escherichia coli, catecholamine signaling, flagellar motility, bacterial virulence, Enterobacteriaceae, intestinal colonization, two-component systems
- MeSH terms
- Gastrointestinal Microbiome, Animals, Catecholamines, Colitis, Escherichia coli, Flagella, Mice, Inbred BALB C, Sulfonamides, Virulence, Gene Expression Regulation, Bacterial, Mice, Knockout, Escherichia coli Proteins, Mice, Quorum Sensing
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