@article{gilfillan_vilander_pan_goh_o'flaherty_feng_fox_lang_greenberg_abdo_et al._2023, title={<i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses}, volume={11}, ISSN={["2076-393X"]}, url={https://www.mdpi.com/2076-393X/11/12/1774}, DOI={10.3390/vaccines11121774}, abstractNote={Rotavirus diarrhea-associated illness remains a major cause of global death in children under five, attributable in part to discrepancies in vaccine performance between high- and low-middle-income countries. Next-generation probiotic vaccines could help bridge this efficacy gap. We developed a novel recombinant Lactobacillus acidophilus (rLA) vaccine expressing rotavirus antigens of the VP8* domain from the rotavirus EDIM VP4 capsid protein along with the adjuvants FimH and FliC. The upp-based counterselective gene-replacement system was used to chromosomally integrate FimH, VP8Pep (10 amino acid epitope), and VP8-1 (206 amino acid protein) into the L. acidophilus genome, with FliC expressed from a plasmid. VP8 antigen and adjuvant expression were confirmed by flow cytometry and Western blot. Rotavirus naïve adult BALB/cJ mice were orally immunized followed by murine rotavirus strain ECWT viral challenge. Antirotavirus serum IgG and antigen-specific antibody-secreting cell responses were detected in rLA-vaccinated mice. A day after the oral rotavirus challenge, fecal antigen shedding was significantly decreased in the rLA group. These results indicate that novel rLA constructs expressing VP8 can be successfully constructed and used to generate modest homotypic protection from rotavirus challenge in an adult murine model, indicating the potential for a probiotic next-generation vaccine construct against human rotavirus.}, number={12}, journal={VACCINES}, author={Gilfillan, Darby and Vilander, Allison C. and Pan, Meichen and Goh, Yong Jun and O'Flaherty, Sarah and Feng, Ningguo and Fox, Bridget E. and Lang, Callie and Greenberg, Harry B. and Abdo, Zaid and et al.}, year={2023}, month={Dec} }
 @article{pan_morovic_hidalgo-cantabrana_roberts_walden_goh_barrangou_2022, title={Genomic and epigenetic landscapes drive CRISPR-based genome editing in Bifidobacterium}, volume={119}, ISSN={["1091-6490"]}, url={https://doi.org/10.1073/pnas.2205068119}, DOI={10.1073/pnas.2205068119}, abstractNote={Significance Genome engineering in Bifidobacterium remains challenging, despite successful CRISPR deployment in other bacteria, hindering the comprehensive understanding of the molecular mechanisms of health-promoting effects. In this study, we adapted existing CRISPR effectors and editing strategies to generate a variety of editing outcomes in B. animalis subsp. lactis. We also showed that the editing efficiency and genome accessibility are shaped by the genomic and epigenetic landscapes, despite their monomorphic genomes. Together, these findings emphasize that strain-to-strain variation can impact the deployment of genome editing and lead to phenotypic and functional differences. This study expands the genome editing platform of Bifidobacterium to enhance their probiotic efficacy and opens opportunities for the engineering of bacterial biotherapeutics.}, number={30}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Pan, Meichen and Morovic, Wesley and Hidalgo-Cantabrana, Claudio and Roberts, Avery and Walden, Kimberly K. O. and Goh, Yong Jun and Barrangou, Rodolphe}, year={2022}, month={Jul} }
 @article{pan_hidalgo-cantabrana_goh_sanozky-dawes_barrangou_2020, title={Comparative Analysis of Lactobacillus gasseri and Lactobacillus crispatus Isolated From Human Urogenital and Gastrointestinal Tracts}, volume={10}, ISSN={["1664-302X"]}, DOI={10.3389/fmicb.2019.03146}, abstractNote={Lactobacillus crispatus and Lactobacillus gasseri are two of the main Lactobacillus species found in the healthy vaginal microbiome and have also previously been identified and isolated from the human gastrointestinal (GI) tract. These two ecological niches are fundamentally different, notably with regards to the epithelial cell type, nutrient availability, environmental conditions, pH, and microbiome composition. Given the dramatic differences between these two environments, we characterized strains within the same Lactobacillus species isolated from either the vaginal or intestinal tract to assess whether they are phenotypically and genetically different. We compared the genomes of the Lactobacillus strains selected in this study for genetic features of interest, and performed a series of comparative phenotypic assays including small intestinal juice and acid resistance, carbohydrate fermentation profiles, lactic acid production, and host interaction with intestinal Caco-2 and vaginal VK2 cell lines. We also developed a simulated vaginal fluid (SVF) to study bacterial growth in a proxy vaginal environment and conducted differential transcriptomic analysis between SVF and standard laboratory MRS medium. Overall, our results show that although strain-specific variation is observed, some phenotypic differences seem associated with the isolation source. We encourage future probiotic formulation to include isolation source and take into consideration genetic and phenotypic features for use at various body sites.}, journal={FRONTIERS IN MICROBIOLOGY}, author={Pan, Meichen and Hidalgo-Cantabrana, Claudio and Goh, Yong Jun and Sanozky-Dawes, Rosemary and Barrangou, Rodolphe}, year={2020}, month={Jan} }