Department of Population Medicine and Diagnostic Sciences
Email: firstname.lastname@example.org; Phone: 607-253-3926
Sponsor: USDA – National Institute of Food and Agriculture (NIFA)
Grant Number: 2014-67015-21697
Title: Regulation of Salmonella Virulence by Intestinal Fatty Acids
Project Amount: $1,629,759
Project Period: 01/01/14-12/31/18
DESCRIPTION (Provided by Applicant): Bacterial foodborne diseases are an important threat to public health and a severe economic burden to animal agriculture. Prominent among these is salmonellosis, which can be acquired from a large variety of foods, including vegetable produce and prepared foods, in addition to animal products. Salmonella outbreaks often occur over wide geographic areas, sickening many and making identification of the contaminated products difficult. Although found in a wide array of foods, Salmonella remains a continual problem because it is so readily carried by domestic animals, which serve as a disease reservoir through their waste products. The traditional solution to this problem, the use of antibiotics, has failed; the great majority of animals used for food in this country receive these with no apparent affect. Thus, there is the need for alternative strategies to control Salmonella carriage in animal agriculture. An often proposed alternative is the use of probiotics, beneficial members of the intestinal microbiota, or prebiotics, dietary supplements designed to support growth of these same beneficial organisms. These products hold promise, but it is not at all clear how, or if, they might reduce Salmonella carriage. To study this, we will investigate the role of fatty acids in preventing Salmonella carriage. These are natural byproducts of the intestinal microbiota, including probiotic organisms, that exist in high concentration within the intestine and that have themselves been studied as prebiotics. The striking finding is that certain fatty acids, specifically acetate and formate, can induce the expression of Salmonella invasion genes known to be important to virulence, while others, namely propionate and butyrate, can repress these same genes. We thus hypothesize that an effective use of dietary manipulation to reduce Salmonella carriage would be to increase the concentration of the repressive fatty acids within the intestinal tract of animals. Our first approach will be to determine at the molecular level the means by which fatty acids function to repress invasion genes. Our preliminary studies indicate that they do so by affecting a central regulator of invasion, HilD, and so we will use a combination of genetic and biochemical means to characterize this control. We will next extend this work to study Salmonella carriage in chickens, an animal that is highly relevant to Salmonella transmission. We will determine the means by which butyric acid, previously shown to function as a prebiotic to reduce Salmonella shedding in chickens, has its effects, using gfp reporter fusions along with assessments of bacterial growth and intestinal pathology. Finally, we will use a pair of animal models of human infection, conventional and antibiotic treated mice, to understand the in vivo expression of invasion genes and the effects that the intestinal environment has upon this. For this approach, and will again use reporter fusions and growth assessments to study the effects of a proposed prebiotic shown to instead exacerbate salmonellosis. The combined outcomes of this study are therefore likely to lead to practical means to control Salmonella in animals and thus to improve food safety.