Influence of an E. coli hyperadherent probiotic on Salmonella intestinal colonization

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Principal Investigator: BRADLEY D JONES
Organization: UNIVERSITY OF IOWA
Fiscal Year: 2024
Award: $77,750
Funding agency: National Institute of Allergy and Infectious Diseases

Project Abstract
Salmonellosis continues to be one of the most important causes of food-borne illness in
the U.S. Furthermore, multiple-antibiotic resistant Salmonella strains are becoming
untreatable infectious diseases. Poultry meat and eggs are major sources of Salmonella
food-borne illness, due to carriage of these bacterial pathogens in the intestinal
microbiome. The NIH goal to reduce Salmonella human infections is directly linked to the
USDA goal of reducing carriage of Salmonella in poultry. While these goals have been
high priorities for many years, current control efforts have been uniformly unsuccessful.
Accordingly, new approaches are needed to address this infectious disease problem in
the United States. The long-term goal of our work is to reduce or eliminate carriage of
Salmonella in poultry flocks. The working hypothesis of this proposal is that an
engineered probiotic strain that expresses a key Salmonella adherence factor, type 1
fimbriae, can outcompete pathogenic Salmonella strains for position in the intestinal
microbiome of poultry. Significant reduction of Salmonella carriage in poultry will
significantly improve the food safety of poultry and will decrease the incidence of
salmonellosis. There are two specific aims in this proposal: 1) To optimize the binding
activity of the type 1 FimH gene expressed in E. coli Nissle 1917, 2) Demonstrate that
the hyper adherent E. coli strain can competitively exclude Salmonella strains from
colonizing the intestinal epithelium of the poultry host. At the completion of this project,
we expect to have demonstrate that an engineered E. coli probiotic strain can
significantly reduce intestinal carriage of Salmonella in chickens. The focus of this
project is to provide an avenue to reduce cases of human salmonellosis and reduce the
human infection risks posed by multiple-antibiotic resistant Gram-negative bacteria.

Terms: <Address><Adherence><Agriculture><Alleles><Allelomorphs><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotic Resistance><Antibiotics><Assay><Bacteria><Bacterial Adhesins><Bacterial Antibiotic Resistance><Binding><Bioassay><Biologic Models><Biological Assay><Biological Models><Cell Body><Cells><Chickens><Clinical><Communicable Diseases><Consumption><Data><Domestic Fowls><E coli><E. coli><Engineered Probiotics><Engineering><Epithelial Cells><Escherichia coli><Exclusion><Food Safety><GI colonization><GI microbiome><Gallus domesticus><Gallus gallus><Gallus gallus domesticus><Gene Cluster><Gene Expression><Genes><Genetics-Mutagenesis><Goals><Gram-Negative Bacteria><Health><Hospital Admission><Hospitalization><Human><Incidence><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Intestinal><Intestines><Invaded><Link><Macrophage><Meat><Mediating><Miscellaneous Antibiotic><Model System><Modern Man><Modified Probiotics><Molecular Interaction><Multi-Drug Resistance><Multidrug Resistance><Multiple Drug Resistance><Multiple Drug Resistant><Mutagenesis><Mutagenesis Molecular Biology><Mφ><NIH><National Institutes of Health><Organism><Pathogenicity><Pathogenicity Factors><Pathogenicity Island><Plasmids><Play><Position><Positioning Attribute><Poultry><Probiotic Engineering><Probiotics><Proteins><Public Health><Receptor Cell><Research><Resistance to Multi-drug><Resistance to Multidrug><Resistance to Multiple Drug><Resistance to antibiotics><Resistant to Multiple Drug><Resistant to antibiotics><Resistant to multi-drug><Resistant to multidrug><Risk Reduction><Role><S enterica serovar Typhimurium><S typhimurium><S. enterica Typhimurium><S. enterica serovar Typhimurium><S. typhimurium><Salmonella><Salmonella enterica Typhimurium><Salmonella enterica serovar Typhimurium><Salmonella infections><Salmonella typhimurium><Salmonellosis><Source><Specificity><Surface><Testing><US Department of Agriculture><USDA><United States><United States Department of Agriculture><United States National Institutes of Health><Virulence><Virulence Factors><Work><adhesin><antibiotic drug resistance><antibiotic resistant><antibiotic resistant bacteria><bacteria pathogen><bacterial antibiotic resistant><bacterial pathogen><bacterial resistance to antibiotic><bowel><carbapenem resistance><carbapenem resistant><combat><cost estimate><cost estimation><digestive tract microbiome><egg><enteric microbiome><food-born illness><food-borne disease><food-borne illness><foodborn illness><foodborne disease><foodborne illness><gastrointestinal microbiome><gastrointestinal tract colonization><gut colonization><gut microbiome><gut-associated microbiome><hatching><human disease><improved><infection risk><intestinal biome><intestinal colonization><intestinal epithelium><intestinal microbiome><living system><multi-drug resistant><multidrug resistant><new approaches><novel approaches><novel strategies><novel strategy><pathogenic bacteria><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><resistance strain><resistance to carbapenem><resistant strain><resistant to carbapenem><risk-reducing><social role><type 1 fimbriae>