Preventing Salmonella Disease and Carriage by Inhibiting Pathogen Virulence

Principal Investigator: Craig Altier

Department of Population Medicine and Diagnostic Sciences
Grant Number: 2022-67017-36558
Title: Preventing Salmonella Disease and Carriage by Inhibiting Pathogen Virulence
Project Amount: $612,000
Project Period: January 2022 to December 2024

DESCRIPTION (provided by applicant): 

Infection of livestock and poultry by Salmonella continues to hobble US agriculture, as disease caused by this pathogen threatens animal life and production, while also necessitating costly measures to prevent its spread to humans. Treatments for this organism have proven futile. Instead, innovative means to control salmonellosis must reduce its colonization of animals, thus preventing transmission and subsequent disease. We have recently identified a rare chemical class that profoundly inhibits the ability of Salmonella to penetrate the intestinal epithelium, a virulence function that is required for both disease and pathogen carriage. Compounds of this class, termed diffusible signal factors (DSFs), are natural products of some bacteria, in which they are used as quorum-sensing signals. We have found that a single gene from one of these species, when expressed in E. coli, causes the recombinant strain to produce and secrete sufficient DSF to prevent neighboring Salmonella from expressing the genes essential for invasion. We thus propose here to make DSF-producing probiotic strains of E. coli and to test them for their ability to reduce Salmonella colonization of animals, by accomplishing these objectives: 1) Determine the effects of recombinant DSF production on Salmonella invasion by defining the structure of expressed DSFs and their potency in preventing invasion; 2) Efficiently produce a recombinant DSF in E.coli, using a characterized probiotic strain, to determine their ability to effectively repress Salmonella invasion-gene expression, and; 3) Use recombinant E. coli as a delivery system to reduce Salmonella colonization using chickens as the relevant agricultural animal model.