Adherent-invasive Escherichia coli pduB drives vitamin B12-dependent colitis in mice
9 affiliations
- 1Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 2Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 3Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 4Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 5Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 6Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 7Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 8Howard Hughes Medical Institute, Dallas, Texas, USA
- 9Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Abstract
Adherent-invasive Escherichia coli (AIEC) are strongly implicated in the pathogenesis of Crohn’s disease, but the virulence factors driving their invasive and pro-inflammatory behavior remain incompletely defined. Here, we demonstrate that vitamin B12 availability modulates pdu-dependent AIEC virulence. The 1,2-propanediol utilization (pdu) operon, which requires vitamin B12 as a cofactor, has previously been associated with bacterial virulence. Here, we validated this association and demonstrated its functional relevance in mouse models of colitis. Deletion of pduB, a structural component of the pdu microcompartment, in the prototypical AIEC strain NRG857c impaired invasion of intestinal epithelial cells without affecting bacterial growth, biofilm formation, or intestinal colonization. In contrast, pduB deletion reduced mucosal association and significantly attenuated colitis in Il10−/− mice. Moreover, loss of pduB protected against AIEC-induced epithelial barrier dysfunction and reduced expression of pro-inflammatory cytokines, including Il6, Il1b, and Tnf-a. Unexpectedly, pduB deletion was associated with elevated host serum vitamin B12 levels, and exogenous vitamin B12 supplementation directly inhibited AIEC invasion in vitro and effectively protected Il10−/− mice from AIEC-induced colitis. Furthermore, vitamin B12-mediated suppression of AIEC invasion and barrier dysfunction was dependent on an intact pdu pathway. Together, these findings establish pduB as a key regulator of AIEC virulence. Our findings identify vitamin B12 availability as a host-modifiable factor that influences AIEC pathogenicity, suggesting potential therapeutic strategies for AIEC-driven intestinal inflammation in Crohn’s disease.
IMPORTANCE: In this study, we demonstrated that vitamin B12 availability modulates a metabolic interaction between adherent-invasive Escherichia coli (AIEC) and the host micronutrient vitamin B12 that influences AIEC epithelial invasion. We confirm that a gene within the 1,2-propanediol utilization pathway (pduB) is critical for AIEC invasion and the development of intestinal inflammation in multiple mouse models. We further identify that vitamin B12, a cofactor for metabolic reactions within the Pdu microcompartment, is altered in the host during infection, suggesting changes in the microbe-host vitamin B12 utilization dynamics. Functionally, we also show that vitamin B12 supplementation significantly inhibited AIEC invasion of epithelial cells in vitro. Lastly, we found that vitamin B12 supplementation provided strong protection against AIEC-induced colitis in Il10−/− mice, preventing weight loss, rectal prolapse, tissue damage, and inflammatory infiltration, even in animals colonized with wild-type AIEC. Broadly, our work highlights vitamin B12 availability as a modifiable host factor that influences AIEC pathogenicity and suggests new therapeutic avenues for therapeutic strategies targeting microbe-nutrient interactions in inflammatory bowel disease.
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BibTeX
@article{khan2026adherentinvasive,
title = {{Adherent-invasive Escherichia coli pduB drives vitamin B12-dependent colitis in mice}},
author = {Shahanshah Khan and Jungyeon Kim and Alexander Lafrance and Sydney Field and Xi Li and Lisa N. Kinch and Kevin J. Forsberg and Tamia A. Harris-Tryon and Qian Cong and Kim Orth and Hans-Christian Reinecker and Josephine Ni},
journal = {mBio},
year = {2026},
month = sep,
doi = {10.1128/mbio.01698-26},
url = {https://doi.org/10.1128/mbio.01698-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Adherent-invasive Escherichia coli pduB drives vitamin B12-dependent colitis in mice
AU - Shahanshah Khan
AU - Jungyeon Kim
AU - Alexander Lafrance
AU - Sydney Field
AU - Xi Li
AU - Lisa N. Kinch
AU - Kevin J. Forsberg
AU - Tamia A. Harris-Tryon
AU - Qian Cong
AU - Kim Orth
AU - Hans-Christian Reinecker
AU - Josephine Ni
PY - 2026
DA - 2026/09/16
JO - mBio
DO - 10.1128/mbio.01698-26
UR - https://doi.org/10.1128/mbio.01698-26
AB - Adherent-invasive Escherichia coli (AIEC) are strongly implicated in the pathogenesis of Crohn’s disease, but the virulence factors driving their invasive and pro-inflammatory behavior remain incompletely defined. Here, we demonstrate that vitamin B12 availability modulates pdu-dependent AIEC virulence. The 1,2-propanediol utilization (pdu) operon, which requires vitamin B12 as a cofactor, has previously been associated with bacterial virulence. Here, we validated this association and demonstrated its functional relevance in mouse models of colitis. Deletion of pduB, a structural component of the pdu microcompartment, in the prototypical AIEC strain NRG857c impaired invasion of intestinal epithelial cells without affecting bacterial growth, biofilm formation, or intestinal colonization. In contrast, pduB deletion reduced mucosal association and significantly attenuated colitis in Il10−/− mice. Moreover, loss of pduB protected against AIEC-induced epithelial barrier dysfunction and reduced expression of pro-inflammatory cytokines, including Il6, Il1b, and Tnf-a. Unexpectedly, pduB deletion was associated with elevated host serum vitamin B12 levels, and exogenous vitamin B12 supplementation directly inhibited AIEC invasion in vitro and effectively protected Il10−/− mice from AIEC-induced colitis. Furthermore, vitamin B12-mediated suppression of AIEC invasion and barrier dysfunction was dependent on an intact pdu pathway. Together, these findings establish pduB as a key regulator of AIEC virulence. Our findings identify vitamin B12 availability as a host-modifiable factor that influences AIEC pathogenicity, suggesting potential therapeutic strategies for AIEC-driven intestinal inflammation in Crohn’s disease. IMPORTANCE: In this study, we demonstrated that vitamin B12 availability modulates a metabolic interaction between adherent-invasive Escherichia coli (AIEC) and the host micronutrient vitamin B12 that influences AIEC epithelial invasion. We confirm that a gene within the 1,2-propanediol utilization pathway (pduB) is critical for AIEC invasion and the development of intestinal inflammation in multiple mouse models. We further identify that vitamin B12, a cofactor for metabolic reactions within the Pdu microcompartment, is altered in the host during infection, suggesting changes in the microbe-host vitamin B12 utilization dynamics. Functionally, we also show that vitamin B12 supplementation significantly inhibited AIEC invasion of epithelial cells in vitro. Lastly, we found that vitamin B12 supplementation provided strong protection against AIEC-induced colitis in Il10−/− mice, preventing weight loss, rectal prolapse, tissue damage, and inflammatory infiltration, even in animals colonized with wild-type AIEC. Broadly, our work highlights vitamin B12 availability as a modifiable host factor that influences AIEC pathogenicity and suggests new therapeutic avenues for therapeutic strategies targeting microbe-nutrient interactions in inflammatory bowel disease.
SN - 2150-7511
ER -