This $2,000,000 federal Project Grant award from the Agency for Healthcare Research and Quality (AHRQ) under the Research on Healthcare Costs, Quality and Outcomes (CFDA 93.226) program supports research to determine if contact precautions should be used for patients colonized with Clostridioides difficile (C. diff). The study aims to evaluate the frequency, location, and amount of environmental C. diff contamination among patients with C. diff colonization compared to those with C. diff...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $261,492 Project Grant (R21AI188339) to Tufts University School of Medicine to study the epigenetic regulation of sporulation in Clostridioides difficile, a major nosocomial pathogen that costs the U.S. healthcare system approximately $5 billion to treat annually. The research aims to identify specific methylation sites that mediate the epigenetic regulation of sporulation in C. difficile, as the CamA DNA...
This Project Grant award, valued at $180,310.00 and funded by the National Institute of Allergy and Infectious Diseases (NIAID) under CFDA 93.855 Allergy and Infectious Diseases Research, supports research on how the Toxin B (TcdB) protein produced by the bacterium Clostridioides difficile interacts with the cell surface receptor CSPG4 to facilitate infection and disrupt wound healing processes. The research aims to determine how TcdB binds to the chondroitin sulfate chains of CSPG4 to...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) provides $222,852 to support research into the regulation of virulence factors in the pathogenic bacterium Clostridioides difficile. The primary objective is to identify and annotate Rho, NusA, and NusG dependent transcriptional terminators in C. difficile to understand how these regulatory factors influence the...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), is for the development of a novel probiotic yeast-based immunotherapy to prevent the transmission of Clostridioides difficile (C. difficile) infections. The $511,553 award will support research to identify and produce engineered yeast strains that secrete bi-specific antibodies targeting a key C. difficile surface protein,...
This $894,552 project grant from the National Institutes of Health's National Institute of Allergy and Infectious Diseases Allergy and Infectious Diseases Research program (CFDA 93.855) will fund research at the University of Nevada, Las Vegas to probe the effect of a high-fat/high-protein diet on Clostridioides difficile infection. Specifically, the researchers will examine how such a diet impacts inflammation, intestinal permeability, and the gut microbiome before and after antibiotic...
This $780,162 Project Grant from the National Institutes of Health's National Institute of Allergy and Infectious Diseases will fund research at Old Dominion University from August 2022 through July 2026 exploring the role of nutrient and stress sensing in regulating Clostridioides difficile physiology and behavior within the host. The research aims to determine how the stringent response regulates disease-relevant bacterial processes and characterize enzymes that mediate alarmone metabolism...
The federal Project Grant award R01AI178776 in the amount of $1,541,024.00 was provided by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) to the University of Notre Dame DU Lac. The grant aims to elucidate the spore germination pathway of the bacterium Clostridioides difficile and develop pharmacological interventions to interrupt the recurrent cycle of C. difficile infection (CDI). Key objectives...
This $502,500 project grant was awarded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855). The award will fund research to elucidate the molecular mechanisms underlying ferrosome organelle biogenesis in the bacterium Clostridioides difficile, which is a leading cause of antibiotic-associated intestinal infections. The research aims to define how the ferrosome system enables C. difficile to adapt to iron...
This $294,244 Project Grant award, funded by the Department of Health and Human Services (DHHS) Agency for Healthcare Research and Quality (AHRQ) under the Research on Healthcare Costs, Quality and Outcomes (CFDA 93.226) program, supports research to identify sepsis phenotypes associated with antibiotic-resistant pathogens. The project aims to leverage machine learning techniques, including large language models applied to clinical notes, to augment electronic health record (EHR) data and define...
MOLECULAR EPIDEMIOLOGY AND SURVEILLANCE OPTIMIZATION OF CLOSTRIDIOIDES DIFFICILE IN ASYMPTOMATIC PATIENTS - PROJECT SUMMARY CLOSTRIDIOIDES DIFFICILE (CD) IS A UBIQUITOUS, SPORE-FORMER AND THE MOST PREVALENT HEALTHCARE- ASSOCIATED INFECTION. WHILE INFECTIONS ARE OFTEN TRIGGERED BY ANTIBIOTICS, PARTICULARLY IN IMMUNOCOMPROMISED INDIVIDUALS, WE KNOW LITTLE ABOUT THE FACTORS AND RISKS FOR TRIGGERING SYMPTOMATIC CD INFECTION (CDI). THE OVERARCHING OBJECTIVE OF DR. CERSOSIMO'S RESEARCH IS TO UNDERSTAND THE DYNAMICS OF CDI IN AT-RISK PATIENT POPULATIONS AND OPTIMIZE TESTING STRATEGIES FOR TOXIN C. DIFFICILE CARRIAGE TO ENABLE SURVEILLANCE IN BROAD CLINICAL SETTINGS. THE PROPOSED RESEARCH USES ADVANCED GENOMIC-EPIDEMIOLOGIC ANALYSES TO ENHANCE OUR UNDERSTANDING OF CDI EPIDEMIOLOGY IN AT-RISK INPATIENTS, IDENTIFIES ASSOCIATIONS AMONG C. DIFFICILE GENOMIC AND ANTIBIOTIC RESISTANCE PROFILES, AND OPTIMIZES CURRENT HOSPITAL CD SURVEILLANCE PROGRAMS FOR DEPLOYMENT TO A DIVERSE RANGE OF HEALTHCARE INSTITUTIONS. AIM 1 APPLIES MOLECULAR EPIDEMIOLOGIC STRATEGIES TO IDENTIFY PATIENT AND STRAIN-SPECIFIC RISKS FOR THE DEVELOPMENT OF CDI. SUBAIM 1A DEFINES THE DYNAMICS OF INFECTION RISK IN ONCOLOGY AND ICU WARDS WITH GENOMIC-EPIDEMIOLOGIC ANALYSES OF CD IN PATIENTS AND USING PATIENT CO-VARIATE DATA OBTAINED FROM THE ELECTRONIC HEALTH RECORD. SUBAIM 1B DEFINES GENOMIC AND PHENOTYPIC DRIVERS OF STRAIN ANTIBIOTIC RESISTANCE AND THEIR CONTRIBUTION TO ASYMPTOMATIC CARRIAGE AND PROGRESSION TO CDI IN INPATIENT ONCOLOGY WARDS VERSUS OTHER ICU SETTINGS. AIM 2 OPTIMIZES TOOLS FOR CD SURVEILLANCE THROUGH THE A) DEVELOPMENT OF A MORE RAPID AND ACCESSIBLE CLINICAL DIAGNOSTICS ASSAY FOR THE IDENTIFICATION OF TOXIN POSITIVE CD AND B) GENERATION OF INFORMATIVE DATA THAT DEMONSTRATES ANTIBIOTIC TRIGGERS OF CD CARRIAGE TO INFORM POPULATION-BASED CDI PREVENTATIVE STRATEGIES IN COLLABORATIONS WITH CLINICAL INFECTION CONTROL AND INFECTIOUS DISEASE PHARMACY TEAMS. DR. CERSOSIMO BRINGS A ONE HEALTH BACKGROUND PER HER PREVIOUS TRAINING IN ANIMAL GUT HEALTH, CLINICAL DIAGNOSTICS, AND FOOD SCIENCE. HER PRIOR EXPERIENCES AND TRAINING GOALS WILL: 1) OPTIMIZE BIOINFORMATIC AND STATISTICAL APPROACHES IN THE ANALYSIS OF C. DIFFICILE GENOMIC DATA, 2) ADVANCE HER UNDERSTANDING OF MICROBIOLOGY, INFECTIOUS DISEASES, EPIDEMIOLOGY THROUGH HANDS-ON LEARNING IN THE HEALTHCARE SETTING, 3) DEVELOP STRATEGIES TO GENERATE, ANALYZE, AND INTERPRET HIGH-DIMENSIONAL GENOMIC AND PHENOTYPIC ANTIBIOTIC RESISTANCE DATA TO INFORM STRAIN GENOMIC LANDSCAPES AND ASSOCIATED HOSPITAL-FOCUSED ANTIBIOGRAMS FOR C. DIFFICILE, AND 4) IMPROVE HER PROFESSIONAL AND LEADERSHIP SKILLS TO PROGRESS AS AN INDEPENDENT INVESTIGATOR STUDYING QUESTIONS IN INFECTIOUS DISEASE GENOMICS AND EPIDEMIOLOGY FROM A ONE HEALTH PERSPECTIVE. HER APPOINTMENTS AT BRIGHAM AND WOMEN'S HOSPITAL AND HARVARD MEDICAL SCHOOL PROVIDE ACCESS TO STATE-OF-THE-ART CLINICAL, LABORATORY, AND COMPUTATIONAL RESOURCES AND AN INTERNATIONALLY RENOWNED MENTORING COMMITTEE WITH EXPERTISE IN C. DIFFICILE EPIDEMIOLOGY, ANTIBIOTIC STEWARDSHIP, GENOMICS, AND HOSPITAL INFECTION SURVEILLANCE. EDUCATIONAL RESOURCES IN INFECTIOUS DISEASE EPIDEMIOLOGY, ADVANCED BIOSTATISTICS, AND CLINICAL MICROBIOLOGY WILL FURTHER ENABLE HER TRAINING GOALS AND CAREER PROGRESSION TO INDEPENDENCE.