Medical Microbiology Commons^™

Enhancing Preparedness: A Genetic Study Of Sar-Cov-2 And Other Microbial Public Health Threats In Wastewater From A College Town, Christian N. Hutchinson

Master's Theses

Problem

The SARS-CoV-2 (COVID-19) pandemic revealed both the systemic vulnerabilities of our healthcare system as well as the importance of timely, localized data for informing public health responses. Traditional testing approaches were essential but often failed to capture the full extent of viral spread, especially in those with mild or asymptomatic conditions that relied on at home testing. This underreporting hindered effective allocation of resources and made developing effective intervention strategies difficult. We also realized the potential for wastewater surveillance to be applied to tracking antimicrobial resistance gene markers. Taken together, this approach should have important implications for improving public …

Enriched Pathways In Gut Microbiome Predict Response To Immune Checkpoint Inhibitor Treatment Across Demographic Regions And Various Cancer Types, Xunhui Cai, Jennifer Y Cho, Lijun Chen, Yufeng Liu, Fenghu Ji, Katia Salgado, Siyi Ge, Dehua Yang, Hui Yu, Jianbo Shao, P Andrew Futreal, Boris Sepesi, Don Gibbons, Yaobing Chen, Guoping Wang, Chao Cheng, Meng Wu, Jianjun Zhang, Ansel Hsiao, Tian Xia

Faculty, Staff and Student Publications

Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore,

Development Of A Proposed Selective Medium For The Isolation And Differentiation Of P. Sordellii, Dimyana Bottros

Honors Undergraduate Theses

Clostridium, a genus of anaerobic, spore-forming bacteria, includes clinically and ecologically significant species like Clostridium difficile and Paeniclostridium sordellii. C. difficile causes antibiotic-associated colitis, while P. sordellii is linked to fatal infections and spontaneous abortions. Recent studies found both species in marine sediments, suggesting their role in environmental and wildlife health disturbances, including the 2013 mass mortality of over 300 manatees in the Indian River Lagoon. However, isolating and differentiating P. sordellii is challenging due to the lack of selective media optimized for its growth. This thesis proposes a novel selective medium tailored to P. sordellii’s physiological …

A Trivalent Protein-Based Pan-Betacoronavirus Vaccine Elicits Cross-Neutralizing Antibodies Against A Panel Of Coronavirus Pseudoviruses, Syamala Rani Thimmiraju, Rakesh Adhikari, Jeanna R Redd, Maria Jose Villar, Jungsoon Lee, Zhuyun Liu, Yi-Lin Chen, Suman Sharma, Amandeep Kaur, Nestor L Uzcategui, Shannon E Ronca, Wen-Hsiang Chen, Jason T Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

Intratumoral Microbiome Of Adenoid Cystic Carcinomas And Comparison With Other Head And Neck Cancers, Tatiana V Karpinets, Yoshitsugu Mitani, Chia-Chi Chang, Xiaogang Wu, Xingzhi Song, Ivonne I Flores, Lauren K Mcdaniel, Yasmine M Hoballah, Fabiana J Veguilla, Renata Ferrarotto, Lauren E Colbert, Nadim J Ajami, Robert R Jenq, Jianhua Zhang, Andrew P Futreal, Adel K El-Naggar

Faculty, Staff and Student Publications

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the …

Medmicromaps, A Novel Decision-Tree Guide For Infectious Diseases Differential Diagnoses, And Evaluation Of Pre- And Post-Pandemic User Engagement By Preclinical Medical Students, Jason Ceballos, Tavsimran Luthra, Lucia Garces-Torres, Valerie Lentz, Jack Nelson, Claudia Carceles-Roman, Ian Holyoak, Jane Harrington

International Journal of Emerging and Disruptive Innovation in Education : VISIONARIUM

Background: Medical education has undergone major changes in the past 5 years to adapt to the digital-centered student population with diverse learning preferences. To address the challenges of shifting delivery modalities, multimedia resources were created to provide interactive e-learning material on infectious diseases for year 2 medical students.

Methods: Medical students at a USA-accredited Caribbean medical school were provided with supplemental e-learning materials including animations, illustrations, diagnostic algorithms aka MedMicroMaps, and Case-Based tutorials. Participants were classified by semester and lecture delivery: In-person: Cohort 1 (n=526); Virtual: Cohort 2 (n=651); and Hybrid: Cohort 3 ( …

Investigating The Role Of The Gut Microbiota On Immune Checkpoint Inhibitor-Mediated Colitis, Taylor Halsey, Robert Jenq

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs) have been revolutionary in the fight against cancer by recruiting the host immune system as an agent for attack on malignant cells. Unfortunately, immune-related adverse events (irAEs), including ICI-mediated colitis (IMC), are common side effects that result from immune cell mediated damage on healthy tissues. Recent studies have highlighted a role for the gut microbiota in modulating ICI-mediated anti-tumor responses, but less is known regarding how the gut microbiota may impact on irAEs. Considering that the gastrointestinal tract harbors thousands of unique microbial species, many of which are known to modulate the immune system, microbes and …

Quorum-Sensing Agr System Of Staphylococcus Aureus Primes Gene Expression For Protection From Lethal Oxidative Stress, Magdalena Podkowik, Andrew I Perault, Gregory Putzel, Andrew Pountain, Jisun Kim, Ashley L Dumont, Erin E Zwack, Robert J Ulrich, Theodora K Karagounis, Chunyi Zhou, Andreas F Haag, Julia Shenderovich, Gregory A Wasserman, Junbeom Kwon, John Chen, Anthony R Richardson, Jeffrey N Weiser, Carla R Nowosad, Desmond S Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J Torres, Bo Shopsin

Faculty, Staff and Student Publications

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic …

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …

Fbpp: Software To Design Pcr Primers And Probes For Nucleic Acid Base Detection Of Foodborne Pathogens, Mohamed A Soliman, Mohamed S Azab, Hala A Hussein, Mohamed M Roushdy, Mohamed N Abu El-Naga

Faculty, Staff and Student Publications

Foodborne pathogens can be found in various foods, and it is important to detect foodborne pathogens to provide a safe food supply and to prevent foodborne diseases. The nucleic acid base detection method is one of the most rapid and widely used methods in the detection of foodborne pathogens; it depends on hybridizing the target nucleic acid sequence to a synthetic oligonucleotide (probes or primers) that is complementary to the target sequence. Designing primers and probes for this method is a preliminary and critical step. However, new bioinformatics tools are needed to automate, specific and improve the design sets to …

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

Global Proteomic Identifies Multiple Cancer-Related Signaling Pathways Altered By A Gut Pathobiont Associated With Colorectal Cancer, Ewa Pasquereau-Kotula, Giulia Nigro, Florent Dingli, Damarys Loew, Patrick Poullet, Yi Xu, Scott Kopetz, Jennifer Davis, Lucie Peduto, Catherine Robbe-Masselot, Philippe Sansonetti, Patrick Trieu-Cuot, Shaynoor Dramsi

Faculty, Staff and Student Publications

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of …

Cellular Dynamics And Disease Outcome Of Type 3 Streptococcus Pneumoniae Clinical Isolates Differ Between Strains, Taylor Rae Plunkett White

Theses and Dissertations (ETD)

Streptococcus pneumoniae is a bacterial pathogen that continues to be a major cause of disease around the world. It is not only the number one cause of bacterial pneumonia but also the cause of about 15% of the deaths of children under 5 around the world. There is a lot of research done on this organism, but with around 100 known serotypes and each one producing a unique capsule, there is still much more to be studied. The Etiology of Pneumonia in the Community (EPIC) study conducted by the CDC observed the burden of hospitalizations caused by pneumonia while determining …

Examining The Pulmonary Response To Repeated Vishniacozyma Victoriae Exposure And Its Association With Allergic Airway Disease, Rachael Erin Rush

Graduate Theses, Dissertations, and Problem Reports (ETD)

Allergic airway diseases such as asthma continue to increase in incidence in industrialized nations like the United States. These diseases are complex inflammatory processes involving numerous cells and mediators and are strongly influenced by fungal exposures. Recent developments in fungal detection methods have highlighted the contribution of Basidiomycota yeast species in indoor environments such as Vishniacozyma (syn. Cryptococcus) victoriae. However, despite the high levels of this yeast detected in indoor environments, very little is known about it or its role in respiratory morbidity. V. victoriae is phylogenetically similar to pathogenic Cryptococcus neoformans but lacks a capsule and is …

Evaluation Of Stratified Antibiograms For Use In Laboratory And Antimicrobial Stewardship, Linsey Donner

Theses & Dissertations

Antibiograms are critical for choosing empiric antimicrobial therapy. Cumulative antibiograms, which aggregate susceptibility data, can mask differences within specific patient subsets or clinical syndromes. This dissertation was done to determine if antibiotic susceptibilities showed substantial differences when comparing stratified antibiograms to cumulative antibiograms.

Antibiotic susceptibility data was retrospectively obtained from Nebraska Medicine January 1, 2017 – December 31, 2019 for Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. The University of Nebraska Medical Center’s web antibiogram clinical decision support tool was used to export the data. Bacteria-antibiotic susceptibility rates of stratified antibiograms …

Loss Of N1-Methylation Of G37 In Trna Induces Ribosome Stalling And Reprograms Gene Expression, Isao Masuda, Jae-Yeon Hwang, Thomas Christian, Sunita Maharjan, Fuad Mohammad, Howard Gamper, Allen R. Buskirk, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

N¹-methylation of G37 is required for a subset of tRNAs to maintain the translational reading-frame. While loss of m¹G37 increases ribosomal +1 frameshifting, whether it incurs additional translational defects is unknown. Here, we address this question by applying ribosome profiling to gain a genome-wide view of the effects of m¹G37 deficiency on protein synthesis. Using E coli as a model, we show that m¹G37 deficiency induces ribosome stalling at codons that are normally translated by m¹G37-containing tRNAs. Stalling occurs during decoding of affected codons at the ribosomal A site, indicating …

Molecular Interactions Of Human Cell Proteins With Sars-Cov-2 Versus Influenza Viruses, Linze Cowman

Honors Thesis

Molecular Interactions of Human Cell Proteins with SARS-CoV-2 versus Influenza

Viruses

Linze Cowman

Director: Victor Huber, Ph.D.

The novel Coronavirus Disease 2019, or COVID- 19, shows considerable similarity to a common influenza infection. Over the past year, innumerable studies have been investigating the Vitus in various capacities, from big-picture public health repercussions to the virus' biochemical interactions with human cells for infection. This research provides invaluable information in the ongoing war against infectious diseases. While the influenza virus is fairly well-understood, much surrounding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear, including its longevity, long-term health effects, methods …

Discovery Of A Bacterial Peptide As A Modulator Of Glp-1 And Metabolic Disease, Catherine Tomaro-Duchesneau, Stephanie L Levalley, Daniel Roeth, Liang Sun, Frank T Horrigan, Markus Kalkum, Joseph M Hyser, Robert A Britton

Faculty, Staff and Students Publications

Early work in rodents highlighted the gut microbiota's importance in metabolic disease, including Type II Diabetes Mellitus (T2DM) and obesity. Glucagon-like peptide-1 (GLP-1), an incretin secreted by L-cells lining the gastrointestinal epithelium, has important functions: promoting insulin secretion, insulin sensitivity, and β-cell mass, while inhibiting gastric emptying and appetite. We set out to identify microbial strains with GLP-1 stimulatory activity as potential metabolic disease therapeutics. Over 1500 human-derived strains were isolated from healthy individuals and screened for GLP-1 modulation by incubating bacterial cell-free supernatants with NCI H716 L-cells. Approximately 45 strains capable of increasing GLP-1 were discovered. All GLP-1 positive …

Factors Affecting Biofilm Formation In Oral Pathogenic Bacteria Of The Red Complex, Sidney Nechacov

Theses and Dissertations (Comprehensive)

Periodontal disease, also known as periodontitis, is a dental disease that is estimated to affect 2.4 billion people worldwide. This disease is characterized by chronic inflammation and bleeding of gums, as well as loss of tooth bone density. Currently, treatments for the disease include dental surgeries and various types of antibiotics, but few are targeted specifically at the Red Complex bacteria which are strongly associated with chronic periodontitis. The Red Complex consists of three bacteria: Tannerella forsythia, Porphyromonas gingivalis and Treponema denticola. Each of these bacteria, are anaerobic oral pathogens that reside in the subgingival pocket adjacent to …

Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe

Department of Biological Sciences Publications

The vast majority of clinical human listeriosis cases are caused by serotype 1/2a, 1/2b, 1/2c, and 4b isolates of Listeria monocytogenes. The ability of L. monocytogenes to establish a systemic listeriosis infection within a host organism relies on a combination of genes that are involved in cell recognition, internalization, evasion of host defenses, and in vitro survival and growth. Recently, whole genome sequencing and comparative genomic analysis have proven to be powerful tools for the identification of these virulence-associated genes in L. monocytogenes. In this study, two serotype 1/2b strains of L. monocytogenes with analogous isolation sources, but …

Changing Diagnostic Methods And Increased Detection Of Verotoxigenic Escherichia Coli, Ireland, Thomas Rice, Noreen Quinn, Roy D. Sleator, Brigid Lucey

Department of Biological Sciences Publications

The recent paradigm shift in infectious disease diagnosis from culture-based to molecular-based approaches is exemplified in the findings of a national study assessing the detection of verotoxigenic Escherichia coli infections in Ireland. The methodologic changes have been accompanied by a dramatic increase in detections of non-O157 verotoxigenic E. coli serotypes.

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …

Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 β-lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings …

A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove

Dartmouth Scholarship

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of …

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …

Smarter Vaccine Design Will Circumvent Regulatory T Cell-Mediated Evasion In Chronic Hiv And Hcv Infection, Leonard Moise, Frances Terry, Andres H. Gutierrez, Ryan Tassone, Phyllis Losikoff, Stephen H. Gregory, Chris Bailey-Kellogg

Dartmouth Scholarship

Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4(+) and CD8(+) T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a T cell receptor (TCR)-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses …

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

The Microbiome In Pediatric Cystic Fibrosis Patients: The Role Of Shared Environment Suggests A Window Of Intervention, Thomas H. Hampton, Deanna M. Green, Garry R. Cutting, Hilary G. Morrison, Mitchell L. Sogin, Alex H. Gifford, Bruce A. Stanton, George A. O’Toole

Dartmouth Scholarship

Cystic fibrosis (CF) is caused by mutations in the CFTR gene that predispose the airway to infection. Chronic infection by pathogens such as Pseudomonas aeruginosa leads to inflammation that gradually degrades lung function, resulting in morbidity and early mortality. In a previous study of CF monozygotic twins, we demonstrate that genetic modifiers significantly affect the establishment of persistent P. aeruginosa colonization in CF. Recognizing that bacteria other than P. aeruginosa contribute to the CF microbiome and associated pathology, we used deep sequencing of sputum from pediatric monozygotic twins and nontwin siblings with CF to characterize pediatric bacterial communities and the …

Human And Helicobacter Pylori Coevolution Shapes The Risk Of Gastric Disease, Nuri Kodaman, Alvaro Pazos, Barbara G. Schneider, M. Blanca Piazuelo, Robertino Mera, Rafal S. Sobota

Dartmouth Scholarship

Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster …

Probiotics: Achieving A Better Regulatory Fit, Diane E. Hoffmann, Claire M. Fraser, Francis Palumbo, Jacques Ravel, Virginia Rowthorn, Jack Schwartz

Faculty Scholarship

In 2007, the National Institutes of Health (NIH) launched the Human Microbiome Project (HMP), a $150 million initiative to characterize the microbial communities found at several different sites on the human body and to analyze the role of these microbes in human health and disease. Many lines of research have demonstrated the significant role of the microbiota in human physiology. The microbiota is involved, for example, in the healthy development of the immune system, prevention of infection from pathogenic or opportunistic microbes, and maintenance of intestinal barrier function. The HMP findings are helping us understand the role and variation of …