Sort
15,273 grants matching “antimicrobial resistance”
Class II MHC Transport and Function
$367,923Clifford V Harding · Case Western Reserve University · R01 · FY2009 · AI
Gene silencing therapeutics for chronic infections in cystic fibrosis
$367,923David Elihu Greenberg · Ut Southwestern Medical Center · R33 · FY2015 · AI
LISTERIA MONOCYTOGENES IS A BACTERIAL FOODBORNE PATHOGEN WHICH REMAINS A MAJOR CAUSE OF DEATHS DUE TO FOODBORNE DISEASE IN THE UNITED STATES. INFECTION CAN RESULT IN INVASIVE, SYSTEMIC ILLNESS (LISTERIOSIS) WITH SEVERE SYMPTOMS AND HIGH CASE FATALITY RATE OF APPROXIMATELY 16%, EVEN UNDER APPROPRIATE ANTIMICROBIAL TREATMENT. IT AFFLICTS PRIMARILY INDIVIDUALS SUFFERING FROM SEVERE IMMUNOCOMPROMISING CONDITIONS, THE ELDERLY, AND PREGNANT WOMEN IN WHOM ILLNESS CAN RESULT IN ABORTIONS AND STILLBIRTHS. LISTERIA HAS BECOME NOTORIOUS FOR ITS CAPACITY TO PERSIST IN FOOD PROCESSING ENVIRONMENTS OVER LONG PERIODS OF TIME, SOMETIMES OVER MANY YEARS. IN SPITE OF IMPROVEMENTS IN LISTERIA SURVEILLANCE AND CONTROL, OUTBREAKS OF FOODBORNE LISTERIOSIS AND MULTIPLE FOOD RECALLS CONTINUE TO TAKE PLACE IN THE UNITED STATES AND OTHER INDUSTRIALIZED NATIONS, SUGGESTING THE NEED FOR IMPROVED INTERVENTIONS. IN THIS PROJECT WE WILL TAKE ADVANTAGE OF RECENT ADVANCES IN THE USE OF CRISPR TECHNOLOGY TOWARDS THE GENETIC ENGINEERING OF VIRUSES (ALSO REFERRED TO AS BACTERIOPHAGE OR PHAGE) SPECIFIC FOR LISTERIA. LISTERIA-SPECIFIC PHAGE HAVE THE CAPACITY TO SERVE AS POWERFUL BIOLOGICAL CONTROLS AGAINST LISTERIA, AND HAVE ALREADY GAINED REGULATORY APPROVAL IN THE UNITED STATES FOR THEIR USE IN FOODS AND FOOD PROCESSING ENVIRONMENTS. HOWEVER, THEIR EFFICACY CAN BE COMPROMISED BY THE FACT THAT CERTAIN STRAINS OF LISTERIA, INCLUDING ALL MEMBERS OF A MAJOR CLONAL GROUP IMPLICATED IN NUMEROUS OUTBREAKS, ARE RESISTANT TO PHAGE. WE WILL EMPLOY AN ARRAY OF MOLECULAR BIOLOGIC PROCEDURES TO ENGINEER THE GENOMES OF LISTERIA-SPECIFIC PHAGE SO THAT THEY ENCODE CRISPR SYSTEMS PROGRAMMED TO DEGRADE HIGHLY-CONSERVED GENES OF LISTERIA MONOCYTOGENES, ESSENTIALLY CAUSING LISTERIA TO SELF-DESTRUCT UPON INFECTION BY THE PHAGE. THE CRISPR SYSTEM WILL BE INTRODUCED IN PHAGE GENOMES WHICH WILL BE ADDITIONALLY MODIFIED TO ALLOW MAXIMUM HOST RANGE, SO THAT LISTERIA STRAINS OF DIVERSE SEROTYPES AND GENOTYPES CAN BE EFFECTIVELY INFECTED AND KILLED. SPECIFIC PROCEDURES WILL BE EMPLOYED TO ALLOW THE PHAGE TO EVADE THE RESISTANCE EXHIBITED BY CERTAIN PROBLEMATIC STRAINS OF LISTERIA MONOCYTOGENES. THE ENGINEERED CRISPR-EQUIPPED PHAGES WILL BE VALIDATED AGAINST A LARGE LISTERIA PANEL INCLUDING STRAINS FROM FOOD PROCESSING ENVIRONMENTS, READY-TO-EAT FOODS AND RECENT OUTBREAKS OF HUMAN LISTERIOSIS. WE EXPECT THAT THE ENGINEERED PHAGE WILL SERVE WELL AS A HIGHLY-TARGETED, EFFECTIVE BIOCONTROL TOOL FOR ELIMINATING PERSISTENT LISTERIA MONOCYTOGENES FROM FOOD-PROCESSING ENVIRONMENTS, THUS SIGNIFICANTLY ENHANCING THE SAFETY OF THE FOOD SUPPLY.
$367,899North Carolina State University · · FY2019 · National Institute of Food and Agriculture
Bile, Biofilms and Salmonella Gallbladder Carriage
$367,875John S Gunn · Ohio State University · R01 · FY2009 · AI
Pathogensis of Bacterial corneal infection
$367,826Gerald B Pier · Brigham And Women'S Hospital · R01 · FY2013 · EY
THE SALMONELLA TYPHIMURIUM SIGMAE REGULON
$367,781Ferric C Fang · University Of Washington · R01 · FY2010 · AI
BETA LACTAMASE MUTATIONS IN ANTIBIOTIC RESISTANCE
$367,775Timothy Palzkill · Baylor College Of Medicine · R01 · FY2013 · AI
CYTOKINE INFLAMMATORY MEDIATORS AND MUCIN REGULATION IN MIDDLE EAR EPITHELIUM
$367,766Joseph E Kerschner · Medical College Of Wisconsin · R01 · FY2007 · DC
Development and implementation of a pediatric AI multi-modal digital stethoscope and respiratory surveillance system in South Africa
$367,680Eric Douglass McCollum · Johns Hopkins University · R21 · FY2023 · HD
VTEU: STI Diagnostic Studies
$367,673Karen Kotloff · University Of Maryland Baltimore · N01 · FY2016 · AI
IFNGR Down Regulation as a Host Target for Therapy of Infectious Diseases
$367,624Laurel L Lenz · University Of Colorado Denver · R33 · FY2015 · AI
Biogenesis of cyclic and phospholipid-linked enterobacterial common antigen
$367,537Angela Marie Mitchell · Texas A&M University · R01 · FY2022 · AI
The role of redox sensing in Listeria monocytogenes pathogenesis
$367,516Michelle Lynne Reniere · University Of Washington · R01 · FY2019 · AI
Targeting MraY: Synthesis and Validation of MraY Inhibitors
$367,500Michio Kurosu · Colorado State University · R01 · FY2010 · AI
Drug-eluting joint implants with synergistic antimicrobial release and risk stratified models of preclinical efficacy testing
$367,366Ebru Oral · Massachusetts General Hospital · R01 · FY2023 · AR
Metals, Drugs and Fungal Pathogens
$367,332Katherine J. Franz · Duke University · R01 · FY2019 · GM
Towards the Development of Engineered Phage Therapeutics against MDR Pathogens
$367,300Sebastien Lemire · C3 Jian, Llc · R33 · FY2020 · AI
Multidrug resistant Acinetobacter baumannii,
$367,115Robert A. Bonomo · Case Western Reserve University · R01 · FY2008 · AI
RIVUR Study
$367,096Tej K Mattoo · Wayne State University · U01 · FY2011 · DK
The transcriptional circuitry controlling biofilm development in Candida albicans
$367,054Alexander D Johnson · University Of California, San Francisco · R01 · FY2014 · AI
The Outer Surface of Vibrio cholerae
$367,043Michael Stephen Trent · University Of Texas At Austin · R01 · FY2010 · AI
STAPHYLOCOCCAL METHICILLIN RESISTANCE LOCUS
$367,022Virginia Commonwealth University · R37 · FY2001 · AI
Influenza A Inhibits TH17 Host Defense Against Bacterial Pneumonia
$366,981John F Alcorn · University Of Pittsburgh At Pittsburgh · R01 · FY2015 · HL
CTCL immunobiology: lessons from alemtuzumab
$366,977Rachael Ann Clark · Brigham And Women'S Hospital · R01 · FY2017 · AR
CTCL immunobiology: lessons from alemtuzumab
$366,977Rachael Ann Clark · Brigham And Women'S Hospital · R01 · FY2016 · AR