Gastroenterology Commons^™

Small Bowel Stomas Are Associated With Higher Risk Of Circulating Food-Specific-Igg Than Patients With Organic Gastrointestinal Conditions And Colostomies, Walker K. Carson, Joseph L. Baumert, Jennifer Clarke, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Objective The effects of food sensitivity can easily be masked by other digestive symptoms in ostomates and are unknown. We investigated food-specific-IgG presence in ostomates relative to participants affected by other digestive diseases.

Design Food-specific-IgG was evaluated for 198 participants with a panel of 109 foods. Immunocompetency status was also tested. Jejunostomates, ileostomates, and colostomates were compared with individuals with digestive tract diseases with inflammatory components (periodontitis, eosinophilic esophagitis, duodenitis, ulcerative colitis, Crohn’s disease, and appendicitis), as well as food malabsorption due to intolerance. A logistic regression model with covariates was used to estimate the effect of the experimental data …

Mapk6-Akt Signaling Promotes Tumor Growth And Resistance To Mtor Kinase Blockade, Qinbo Cai, Wolong Zhou, Wei Wang, Bingning Dong, Dong Han, Tao Shen, Chad J Creighton, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Mitogen-activated protein kinase 6 (MAPK6) is an atypical MAPK. Its function in regulating cancer growth remains elusive. Here, we reported that MAPK6 directly activated AKT and induced oncogenic outcomes. MAPK6 interacted with AKT through its C34 region and the C-terminal tail and phosphorylated AKT at S473 independent of mTORC2, the major S473 kinase. mTOR kinase inhibitors have not made notable progress in the clinic. Our identified MAPK6-AKT axis may provide a major resistance pathway. Besides repressing growth, inhibiting MAPK6 sensitized cancer cells to mTOR kinase inhibitors. MAPK6 overexpression is associated with decreased overall survival and the survival of patients with …

The Sulfur Microbial Diet Is Associated With Increased Risk Of Early-Onset Colorectal Cancer Precursors, Long H. Nguyen, Yin Cao, Jinhee Hur, Raaj S. Mehta, Daniel R. Sikavi, Yiqing Wang, Wenjie Ma, Kana Wu, Mingyang Song, Edward L. Giovannucci, Eric B. Rimm, Walter C. Willett, Wendy S. Garrett, Jacques Izard, Curtis Huttenhower, Andrew T. Chan

Food for Health: Publications

Background and aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H₂S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking.

Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses’ Health Study II …

Intestinal Dysbiosis – A New Treatment Target In The Prevention Of Colorectal Cancer, Florinela-Andrada Dumitru, Sergiu Ioan Micu, Roxana Emanuela Popoiag, Marilena Musat, Andreea Daniela Caloian, Valentin Calu, Vlad Denis Constantin, Daniela Gabriela Balan, Cornelia Nitipir, Florin Enache

Journal of Mind and Medical Sciences

The gastrointestinal microbiome contains at least 100 trillion microorganisms (bacteria, viruses, fungi), whose distribution varies from the mouth to the rectum spatially and temporally throughout one's lifetime. The microbiome benefits from advancing research due to its major role in human health. Studies indicate that its functions are immunity, metabolic processes and mucosal barrier. The disturbances of these functions, dysbiosis, influence physiology, lead to diabetes, inflammatory bowel disease, obesity and colon tumorigenesis. The third most common form of cancer, colorectal cancer, is the result of many factors and genes, and although the link between dysbiosis and this type of cancer is …

Output Consistency Scale To Standardize Ostomate Output Description In Clinical Practice And Studies, Lisa Whisenhunt, Linda Xu, Fan Yang, Jacques Izard

Food for Health: Publications

Stool descriptors have become popular due to the large diffusion of the Bristol Stool Form Scale (BSFS) via clinical studies, clinical trials, and social media. The applications have been numerous and centered around standardization of terminology that can be used by health care professionals and patients alike, as well as individuals interested in their wellness and the associated partners in the wellness industry. For a portion of the population, the digestive content is rerouted to an external manufactured pouch or bag, making the use of the BSFS visual descriptors of stool difficult. From day one post-resection surgery, ostomates are challenged …

Habitual Sleep Duration And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Pilot Study, Ritwick Agrawal, Nadim J Ajami, Sonal Malhotra, Liang Chen, Donna L White, Amir Sharafkhaneh, Kristi L Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

We examined the association between the colonic adherent microbiota and nocturnal sleep duration in humans. In a cross-sectional study, 63 polyp-free adults underwent a colonoscopy and donated 206 mucosal biopsies. The gut microbiota was profiled using the 16S rRNA gene sequencing targeting the V4 region. The sequence reads were processed using UPARSE and DADA2, respectively. Lifestyle factors, including sleep habits, were obtained using an interviewer-administered questionnaire. We categorized the participants into short sleepers (<6 h per night; n = 16) and normal sleepers (6–8 h per night; n = 47) based on self-reported data. Differences in bacterial biodiversity and the taxonomic relative abundance …

Categorization Of Orthologous Gene Clusters In 92 Ascomycota Genomes Reveals Functions Important For Phytopathogenicity, Daniel Peterson, Tang Li, Ana M. Calvo, Yanbin Yin

Food for Health: Publications

Phytopathogenic Ascomycota are responsible for substantial economic losses each year, destroying valuable crops. The present study aims to provide new insights into phytopathogenicity in Ascomycota from a comparative genomic perspective. This has been achieved by categorizing orthologous gene groups (orthogroups) from 68 phytopathogenic and 24 non-phytopathogenic Ascomycota genomes into three classes: Core, (pathogen or non-pathogen) group-specific, and genome-specific accessory orthogroups. We found that (i) ~20% orthogroups are group-specific and accessory in the 92 Ascomycota genomes, (ii) phytopathogenicity is not phylogenetically determined, (iii) group-specific orthogroups have more enriched functional terms than accessory orthogroups and this trend is particularly evident in phytopathogenic …

The Chromosome-Level Genome Of Dragon Fruit Reveals Whole-Genome Duplication And Chromosomal Co-Localization Of Betacyanin Biosynthetic Genes, Jinfang Zheng, Lyndel W. Meinhardt, Ricardo Goenaga, Dapeng Zhang, Yanbin Yin

Food for Health: Publications

Dragon fruits are tropical fruits economically important for agricultural industries. As members of the family of Cactaceae, they have evolved to adapt to the arid environment. Here we report the draft genome of Hylocereus undatus, commercially known as the white-fleshed dragon fruit. The chromosomal level genome assembly contains 11 longest scaffolds corresponding to the 11 chromosomes of H. undatus. Genome annotation of H. undatus found ~29,000 protein-coding genes, similar to Carnegiea gigantea (saguaro). Whole-genome duplication (WGD) analysis revealed a WGD event in the last common ancestor of Cactaceae followed by extensive genome rearrangements. The divergence …

Characterization Of Two Zygnema Strains (Zygnema Circumcarinatum Sag 698-1a And Sag 698-1b) And A Rapid Method To Estimate Nuclear Genome Size Of Zygnematophycean Green Algae, Xuehuan Feng, Andreas Holzinger, Charlotte Permann, Dirk Anderson, Yanbin Yin

Food for Health: Publications

Zygnematophyceae green algae (ZGA) have been shown to be the closest relatives of land plants. Three nuclear genomes (Spirogloea muscicola, Mesotaenium endlicherianum, and Penium margaritaceum) of ZGA have been recently published, and more genomes are underway. Here we analyzed two Zygnema circumcarinatum strains SAG 698-1a (mating +) and SAG 698-1b (mating −) and found distinct cell sizes and other morphological differences. The molecular identities of the two strains were further investigated by sequencing their 18S rRNA, psaA and rbcL genes. These marker genes of SAG 698-1a were surprisingly much more similar to Z. cylindricum (SAG 698-2) than to SAG 698-1b. …

Characterization Of Two Zygnema Strains (Zygnema Circumcarinatum Sag 698-1a And Sag 698-1b) And A Rapid Method To Estimate Nuclear Genome Size Of Zygnematophycean Green Algae, Xuehuan Feng, Andreas Holzinger, Charlotte Permann, Dirk Anderson, Yanbin Yin

Food for Health: Publications

Zygnematophyceae green algae (ZGA) have been shown to be the closest relatives of land plants. Three nuclear genomes (Spirogloea muscicola, Mesotaenium endlicherianum, and Penium margaritaceum) of ZGA have been recently published, and more genomes are underway. Here we analyzed two Zygnema circumcarinatum strains SAG 698-1a (mating +) and SAG 698-1b (mating −) and found distinct cell sizes and other morphological differences. The molecular identities of the two strains were further investigated by sequencing their 18S rRNA, psaA and rbcL genes. These marker genes of SAG 698-1a were surprisingly much more similar to Z. cylindricum (SAG 698-2) than to SAG 698-1b. …

Characterization Of Two Zygnema Strains (Zygnema Circumcarinatum Sag 698-1a And Sag 698-1b) And A Rapid Method To Estimate Nuclear Genome Size Of Zygnematophycean Green Algae, Xuehuan Feng, Andreas Holzinger, Charlotte Permann, Dirk Anderson, Yanbin Yin

Food for Health: Publications

Zygnematophyceae green algae (ZGA) have been shown to be the closest relatives of land plants. Three nuclear genomes (Spirogloea muscicola, Mesotaenium endlicherianum, and Penium margaritaceum) of ZGA have been recently published, and more genomes are underway. Here we analyzed two Zygnema circumcarinatum strains SAG 698-1a (mating +) and SAG 698-1b (mating −) and found distinct cell sizes and other morphological differences. The molecular identities of the two strains were further investigated by sequencing their 18S rRNA, psaA and rbcL genes. These marker genes of SAG 698-1a were surprisingly much more similar to Z. cylindricum (SAG 698-2) than to SAG 698-1b. …

Comparisons Of Oral, Intestinal, And Pancreatic Bacterial Microbiomes In Patients With Pancreatic Cancer And Other Gastrointestinal Diseases, Mei Chung, Naisi Zhao, Richard Meier, Devin C. Koestler, Guojun Wu, Erika De Castillo, Bruce J. Paster, Kevin Charpentier, Jacques Izard, Karl T. Kelsey, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: Oral microbiota is believed to play important roles in systemic diseases, including cancer. Methods: We collected oral samples (tongue, buccal, supragingival, and saliva) and pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S rRNA genes using high-throughput DNA sequencing.

Results: Bray–Curtis plot showed clear separations between bacterial communities in the oral cavity and those in intestinal and pancreatic tissue samples. PERMANOVA tests indicated that bacterial communities from buccal samples were similar to supragingival and saliva samples, and pancreatic duct samples were similar to pancreatic tumor samples, but all other samples were significantly different from each …

The Trait Repertoire Enabling Cyanobacteria To Bloom Assessed Through Comparative Genomic Complexity And Metatranscriptomics, Huansheng Cao, Yohei Shimura, Morgan M. Steffen, Zhou Yang, Jingrang Lu, Allen Joel, Landon Jenkins, Masanobu Kawachi, Yanbin Yin, Ferran Garcia-Pichel

Food for Health: Publications

Water bloom development due to eutrophication constitutes a case of niche specialization among planktonic cyanobacteria, but the genomic repertoire allowing bloom formation in only some species has not been fully characterized. We posited that the habitat relevance of a trait begets its underlying genomic complexity, so that traits within the repertoire would be differentially more complex in species successfully thriving in that habitat than in close species that cannot. To test this for the case of bloom-forming cyanobacteria, we curated 17 potentially relevant query metabolic pathways and five core pathways selected according to existing ecophysiological literature. The available 113 genomes …

Alteration Of The Gut Microbiome In Normal And Overweight School Children From Selangor With Lactobacillus Fermented Milk Administration, Narcisse Joseph, Jonathan B. Clayton, Susan L. Hoops, Carter A. Linhardt, Amalia Mohd Hashim, Barakatun Nisak Mohd Yusof, Suresh Kumar, Syafinaz Amin Nordin

Food for Health: Publications

Childhood obesity is a serious public health problem worldwide. Perturbations in the gut microbiota composition have been associated with the development of obesity in both children and adults. Probiotics, on the other hand, are proven to restore the composition of the gut microbiome which helps reduce the development of obesity. However, data on the effect of probiotics on gut microbiota and its association with childhood obesity is limited. This study aims to determine the effect of probiotics supplement intervention on gut microbiota profiles in obese and normal-weight children. A total of 37 children, 17 normal weight, and 20 overweight school …

Stool Microbiome, Ph And Short/Branched Chain Fatty Acids In Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, Or Human Milk Through Two Months Of Age, Car Reen Kok, Bradford Brabec, Maciej Chichlowski, Cheryl L. Harris, Nancy Moore, Jennifer L. Wampler, Jon Vanderhoof, Devin Rose, Robert Hutkins

Food for Health: Publications

CRISPR–Cas is an anti-viral mechanism of prokaryotes that has been widely adopted for genome editing. To make CRISPR–Cas genome editing more controllable and safer to use, anti-CRISPR proteins have been recently exploited to prevent excessive/prolonged Cas nuclease cleavage. Anti-CRISPR (Acr) proteins are encoded by (pro)phages/(pro)viruses, and have the ability to inhibit their host’s CRISPR–Cas systems. We have built an online database AcrDB (http://bcb.unl.edu/AcrDB) by scanning ∼19 000 genomes of prokaryotes and viruses with AcrFinder, a recently developed AcrAca (Acr-associated regulator) operon prediction program. Proteins in Acr-Aca operons were further processed by two machine learning-based programs (AcRanker and PaCRISPR) to obtain …

Mucosa-Associated Microbiota In Barrett’S Esophagus, Dysplasia, And Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls, Shajan Peter, Amanda Pendergraft,, William Vanderpol, Mel Wilcox, Kondal R. Kyanam Kabir Baig, Casey Morrow, Jacques Izard, Peter J. Mannon

Department of Food Science and Technology: Faculty Publications

Introduction: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett’s microbiota could link to risk factors, providing risk of progression to neoplasia.

Methods: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria …

Metaproteomic Analysis Of Human Gut Microbiome In Digestive And Metabolic Diseases, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Metaproteomics, as a subfield of proteomics, has quickly emerged as a pivotal tool for global characterization of a microbiome system at a functional level. It has been increasingly applied in studying human digestive and metabolic diseases, and provides information-rich data to identify the dysbiosis of human gut microbiome related to healthy or disease states to elucidate the molecular events underlying host-microbiota interplays. While significant technical challenges still exist, this emerging technology has been demonstrated to provide essential information in interrogating functional changes in the human gut microbiome, complementary to metagenomics and metatranscriptomics. This chapter overviews the overall metaproteomic work flow …

An In Vitro Enrichment Strategy For Formulating Synergistic Synbiotics, Car Reen Kok, David Fabian Gomez Quintero, Clement Niyirora, Devin Rose, Amanda Li, Robert Hutkins

Food for Health: Publications

ABSTRACT Research on the role of diet on gut and systemic health has led to considerable interest toward identifying novel therapeutic modulators of the gut microbiome, including the use of prebiotics and probiotics. However, various host responses have often been reported among many clinical trials. This is in part due to competitive exclusion as a result of the absence of ecological niches as well as host mediated constraints via colonization resistance. In this research, we developed a novel in vitro enrichment (IVE) method for isolating autochthonous strains that can function as synergistic synbiotics and overcome these constraints. The method relied …

Experimental Evaluation Of The Importance Of Colonization History In Early-Life Gut Microbiota Assembly, Inés Martínez, Maria X. Maldonado-Gomez, João Carlos Gomes-Neto, Hatem Kittana, Hua Ding, Robert J. Schmaltz, Payal Joglekar, Roberto Jiménez Cardona, Nathan L Marsteller, Steven W. Kembel, Andrew K. Benson, Daniel A. Peterson, Amanda Ramer-Tait, Jens C. Walter

Department of Food Science and Technology: Faculty Publications

The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in Rag1^-/- mice, suggesting that the adaptive immune system …

Considerations For Best Practices In Studies Of Fiber Or Other Dietary Components And The Intestinal Microbiome, David M. Klurfeld, Cindy D. Davis, Robert W. Karp, Emma Allen-Vercoe, Eugene B. Chang, Benoit Chassaing, George C. Fahey Jr, Bruce R. Hamaker, Hannah D. Holscher, Johanna W. Lampe, Andre Marette, Eric Martens, Stephen J. O'Keefe, Devin J. Rose, Maria Saarela, Barbara O. Schneeman, Joanne L. Slavin, Justin L. Sonnenburg, Kelly S. Swanson, Gary D. Wu, Christopher J. Lynch

Food for Health: Publications

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. Am J Physiol Endocrinol Metab 315: E1087–E1097, 2018. First published August 21, 2018; doi:10.1152/ajpendo.00058.2018.—A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is …

Intestinal Permeability And Microbial Dysbiosis In Acute Coronary Syndrome (Miacs Study), Tarik Z. Alhmoud

Biomedical Sciences ETDs

Background: Acute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Metabolic syndrome and obesity are major risk factors for atherosclerosis and ACS. Dysbiosis plays an important role in metabolic syndrome and obesity. Studies show a markedly increased risk of heart attacks in patients with high levels of the pro-atherogenic metabolite trimethylamine-N-Oxide (TMAO). TMAO is produced by the intestinal microbial flora through metabolism of dietary phospholipids; Gram-negative bacteria (Phylum Proteobacteria) is the major source of TMAO metabolism. Patients with obesity and metabolic syndrome have a defective intestinal tight-junctional (TJ) barrier, which allows paracellular permeation of luminal antigens such …

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Monir Ejemal, Chelsea A. Rapp, William D. Thomas Jr, Eric J. Sundberg, Zhiping Weng, Yang Wang

Food for Health: Publications

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as …

How An Alloreactive T-Cell Receptor Achieves Peptide And Mhc Specificity, Yuan Wang, Nishant K. Singh, Timothy T. Spear, Lance M. Hellman, Kurt H. Piepenbrink, Rachel H. Mcmahan, Hugo R. Rosen, Craig W. Vander Kooi, Michael I. Nishimura, Brian M. Baker

Food for Health: Publications

T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2− individual …

Motility And Adhesion Through Type Iv Pili In Gram-Positive Bacteria, Kurt H. Piepenbrink, Eric J. Sundberg

Food for Health: Publications

Type IV pili are hair-like bacterial surface appendages that play a role in diverse processes such as cellular adhesion, colonization, twitching motility, biofilm formation, and horizontal gene transfer. These extracellular fibers are composed exclusively or primarily of many copies of one or more pilin proteins, tightly packed in a helix so that the highly hydrophobic amino-terminus of the pilin is buried in the pilus core. Type IV pili have been characterized extensively in Gram-negative bacteria, and recent advances in high-throughput genomic sequencing have revealed that they are also widespread in Gram-positive bacteria. Here, we review the current state of knowledge …

A Generalized Framework For Computational Design And Mutational Scanning Of T-Cell Receptor Binding Interfaces, Timothy P. Riley, Cory M. Ayres, Lance M. Hellman, Nishant K. Singh, Michael Cosiano, Jennifer M. Cimons, Michael J. Anderson, Kurt H. Piepenbrink, Brian G. Pierce, Zhiping Weng, Brian M. Baker

Food for Health: Publications

T-cell receptors (TCRs) have emerged as a new class of therapeutics, most prominently for cancer where they are the key components of new cellular therapies as well as soluble biologics. Many studies have generated high affinity TCRs in order to enhance sensitivity. Recent outcomes, however, have suggested that fine manipulation of TCR binding, with an emphasis on specificity may be more valuable than large affinity increments. Structure-guided design is ideally suited for this role, and here we studied the generality of structure-guided design as applied to TCRs. We found that a previous approach, which successfully optimized the binding of a …

Structural Diversity In The Type Iv Pili Of Multidrug-Resistant Acinetobacter, Kurt H. Piepenbrink, Erik Lillehoj, Christian M. Harding, Jason W. Labonte, Xiaotong Zuo, Chelsea A. Rapp, Robert S. Munson Jr, Simeon E. Goldblum, Mario F. Feldman, Jeffrey J. Gray, Eric J. Sundberg

Food for Health: Publications

Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections. A. baumannii expresses a variety of virulence factors, including type IV pili, bacterial extracellular appendages often essential for attachment to host cells. Here, we report the high resolution structures of the major pilin subunit, PilA, from three Acinetobacter strains, demonstrating thatA. baumannii subsets produce morphologically distinct type IV pilin glycoproteins. We examine the consequences of this heterogeneity for protein folding and assembly as well as host-cell adhesion by Acinetobacter. Comparisons of genomic and structural data with pilin proteins from …

The Neu1-Selective Sialidase Inhibitor, C9- Butyl-Amide-Dana, Blocks Sialidase Activity And Neu1-Mediated Bioactivities In Human Lung In Vitro And Murine Lung In Vivo, Sang W. Hyun, Anguo Liu, Zhenguo Liu, Alan S. Cross, Avelino C. Verceles, Sadagopan Magesh, Yadagiri Kommagalla, Chandrababunaidu Kona, Hiromune Ando, Irina G. Luzina, Sergei P. Atamas, Kurt H. Piepenbrink, Eric J. Sundberg, Wei Guang, Hideharu Ishida, Erik P. Lillehoj, Simeon E. Goldblum

Food for Health: Publications

Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-Nacetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of …

Type Iv Pili Promote Early Biofilm Formation By Clostridium Difficile, Grace A. Maldarelli, Kurt H. Piepenbrink, Alison J. Scott, Jeffrey A. Freiberg, Yang Song, Yvonee Achermann, Robert K. Ernst, Mark E. Shirtliff, Eric J. Sundberg, Michael S. Donnenberg, Erik C. Von Rosenvinge

Food for Health: Publications

Increasing morbidity and mortality from Clostridium difficile infection (CDI) present an enormous challenge to healthcare systems. Clostridium difficile express type IV pili (T4P), but their function remains unclear. Many chronic and recurrent bacterial infections result from biofilms, surface-associated bacterial communities embedded in an extracellular matrix. CDI may be biofilm mediated; T4P are important for biofilm formation in a number of organisms. We evaluate the role of T4P in C. difficile biofilm formation using RNA sequencing, mutagenesis and complementation of the gene encoding the major pilin pilA1, and microscopy. RNA sequencing demonstrates that, in comparison to other growth phenotypes, C. difficile …

Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, Laura E. Fitzgerald

Biological Sciences Undergraduate Honors Theses

Clostridium difficile (C. difficile) is a gram-positive bacterium that comprises part of the healthy human gut microbiome. When it gains sufficient access to peptides, C. difficile flourishes and releases tissue-damaging toxins, which cause inflammation of the colon that can develop into a Clostridium difficile Infection (CDI).¹⁰ The Ivey Laboratory believes that the best tactic in preventing CDIs is stopping peptide ingestion, which theoretically could be accomplished by manipulating the oligopeptide permease (App) system.⁷ In order to verify that altering the App system would successfully impede peptide uptake, first the expression of the app Promoter Region ( …

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …