Publications

@article{thomas_clostridioides_2025,

title = {Clostridioides difficile toxins alter host metabolic pathway and bile acid homeostasis gene expression in colonic epithelium},

author = {Stephanie A. Thomas and Colleen M. Pike and Cypress E. Perkins and Sean T. Brown and Xochilt M. Espinoza Jaen and Arthur S. McMillan and Casey M. Theriot},

url = {https://journals.asm.org/doi/full/10.1128/iai.00150-25},

doi = {10.1128/iai.00150-25},

year  = {2025},

date = {2025-06-30},

urldate = {2025-06-30},

journal = {Infection and Immunity},

volume = {93},

number = {8},

pages = {e00150–25},

note = {Publisher: American Society for Microbiology},

keywords = {intestinal microenvironment, microbiome},

pubstate = {published},

tppubtype = {article}

}

@article{corte_morphogenesis_2024,

title = {Morphogenesis of bacterial colonies in polymeric environments},

author = {Sebastian Gonzalez La Corte and Corey A. Stevens and Gerardo Cárcamo-Oyarce and Katharina Ribbeck and Ned S. Wingreen and Sujit S. Datta},

url = {https://www.science.org/doi/10.1126/sciadv.adq7797},

doi = {10.1126/sciadv.adq7797},

year  = {2025},

date = {2025-01-17},

urldate = {2024-04-22},

journal = {Science Advances},

volume = {11},

number = {3},

issue = {3},

pages = {eadq7797},

publisher = {bioRxiv},

abstract = {Many bacteria live in polymeric fluids, such as mucus, environmental polysaccharides, and extracellular polymers in biofilms. However, lab studies typically focus on cells in polymer-free fluids. Here, we show that interactions with polymers shape a fundamental feature of bacterial life—how they proliferate in space in multicellular colonies. Using experiments, we find that when polymer is sufficiently concentrated, cells generically and reversibly form large serpentine “cables” as they proliferate. By combining experiments with biophysical theory and simulations, we demonstrate that this distinctive form of colony morphogenesis arises from an interplay between polymer-induced entropic attraction between neighboring cells and their hindered ability to diffusely separate from each other in a viscous polymer solution. Our work thus reveals a pivotal role of polymers in sculpting proliferating bacterial colonies, with implications for how they interact with hosts and with the natural environment, and uncovers quantitative principles governing colony morphogenesis in such complex environments.},

note = {Pages: 2024.04.18.590088 

Section: New Results},

keywords = {microbiome, Mucus},

pubstate = {published},

tppubtype = {article}

}

@article{sarma_design_2023,

title = {Design of 8-mer Peptides that Block Clostridioides difficile Toxin A in Intestinal Cells},

author = {Sudeep Sarma and Carly M. Catella and Ellyce T. San Pedro and Xingqing Xiao and Deniz Durmusoglu and Stefano Menegatti and Nathan Crook and Scott T. Magness and Carol K. Hall},

doi = {10.1101/2023.01.10.523493},

year  = {2023},

date = {2023-01-12},

urldate = {2023-01-12},

pages = {2023.01.10.523493},

abstract = {Clostridioides difficile ( C. diff .) is a bacterium that causes severe diarrhea and inflammation of the colon. The pathogenicity of C. diff . infection is derived from two major toxins, toxins A (TcdA) and B (TcdB). Peptide inhibitors that can be delivered to the gut to inactivate these toxins are an attractive therapeutic strategy. In this work, we present a new approach that combines a pep tide b inding d esign algorithm (PepBD), molecular-level simulations, rapid screening of candidate peptides for toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block the glucosyltransferase activity of TcdA by targeting its glucosyltransferase domain (GTD). Using PepBD and explicit-solvent molecular dynamics simulations, we identified seven candidate peptides, SA1-SA7. These peptides were selected for specific TcdA GTD binding through a custom solid-phase peptide screening system, which eliminated the weaker inhibitors SA5-SA7. The efficacies of SA1-SA4 were then tested using a trans-epithelial electrical resistance (TEER) assay on monolayers of the human gut epithelial culture model. One peptide, SA1, was found to block TcdA toxicity in primary-derived human jejunum (small intestinal) and colon (large intestinal) epithelial cells. SA1 bound TcdA with a K D of 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR). 

SIGNIFICANCE STATEMENT: Infections by Clostridioides difficile , a bacterium that targets the large intestine (colon), impact a significant number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can inhibit the biocatalytic activity of these toxins represent a promising strategy to prevent and treat C. diff . infection. We describe an approach that combines a Peptide B inding D esign (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in small intestinal and colon epithelial cells. Importantly, our designed peptide, SA1, bound toxin A with nanomolar affinity and blocked toxicity in colon cells.},

keywords = {Adverse events, epithelial barrier, In vitro model, inflammatory bowel disease, intestinal organoids, intestinal stem cells, microbiome},

pubstate = {published},

tppubtype = {article}

}

@article{lemmens_drug_2021,

title = {Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring},

author = {Glenn Lemmens and Arno Van Camp and Stephanie Kourula and Tim Vanuytsel and Patrick Augustijns},

url = {https://www.mdpi.com/1999-4923/13/2/161},

doi = {10.3390/pharmaceutics13020161},

issn = {1999-4923},

year  = {2021},

date = {2021-01-26},

urldate = {2021-01-26},

journal = {Pharmaceutics},

volume = {13},

number = {2},

pages = {161},

abstract = {The increasing prevalence of colonic diseases calls for a better understanding of the various colonic drug absorption barriers of colon-targeted formulations, and for reliable in vitro tools that accurately predict local drug disposition. In vivo relevant incubation conditions have been shown to better capture the composition of the limited colonic fluid and have resulted in relevant degradation and dissolution kinetics of drugs and formulations. Furthermore, drug hurdles such as efflux transporters and metabolising enzymes, and the presence of mucus and microbiome are slowly integrated into drug stability- and permeation assays. Traditionally, the well characterized Caco-2 cell line and the Ussing chamber technique are used to assess the absorption characteristics of small drug molecules. Recently, various stem cell-derived intestinal systems have emerged, closely mimicking epithelial physiology. Models that can assess microbiome-mediated drug metabolism or enable coculturing of gut microbiome with epithelial cells are also increasingly explored. Here we provide a comprehensive overview of the colonic physiology in relation to drug absorption, and review colon-targeting formulation strategies and in vitro tools to characterize colonic drug disposition.},

note = {Number: 2 

Publisher: Multidisciplinary Digital Publishing Institute},

keywords = {colon drug delivery, colonic drug disposition, colonic physiology, drug absorption, drug metabolising enzymes ({DME}), intestinal in vitro models, microbiome, microphysiological systems ({MPS})},

pubstate = {published},

tppubtype = {article}

}