Research

Sulfites are widely distributed reactive sulfur species that play an important role in all organisms’ health. They are endogenously produced by all life forms during breakdown and synthesis of cysteine and methionine. Sulfites are present in many of the foods we eat, both naturally and as additives used to control spoilage. In addition, they are produced by activated neutrophils as a part of the innate immune response to infection. Sulfites can kill bacteria by cleaving DNA, damaging proteins, and oxidizing lipids. Therefore, resisting the toxic effects of sulfites is key for foodborne bacterial pathogens to survive in foods and during infection. Ongoing work in our laboratory is studying how Salmonella responds to sulfites to activate the sulfite stress response.

Non-typhoidal Salmonellae (NTS) can colonize and cause disease in all species of mammals. Disease is spread by consumption of contaminated food, water, or direct contact with individuals shedding the organism. In addition to colonizing mammals, NTS can also colonize birds and reptiles without causing disease, can colonize plants, and can create biofilms on abiotic surfaces to survive in the environment. The combination of broad host range and many strategies allowing for environmental persistence makes NTS very difficult to eradicate. Salmonella Typhimurium responds to host and microbial metabolites to stimulate either its virulence or biofilm paradigms. Ongoing projects in the laboratory study how byproducts of host and microbe amino acid metabolism alter Salmonella gene expression to facilitate its transition between the host and the environment.

Neutrophils are innate immune cells that are on the front line defending the host against invading pathogens. Unlike many other pathogens, Salmonella relies on neutrophils to colonize the gut. Neutrophilic inflammation kills competing resident microbes allowing Salmonella to grow in the gut to reach sufficient numbers for efficient transmission between hosts. Paradoxically, without functioning neutrophils, Salmonella infection causes lethal sepsis. We previously found that expression of Salmonella virulence genes (type-3 secretion system-1 and flagellar motility) are agonists of the neutrophil respiratory burst. We hypothesize that heterogeneity of Salmonella gene expression within the gut allows a portion of the population of Salmonella to thrive during intestinal inflammation. Our ongoing studies seek to understand how Salmonella modulates the magnitude of the neutrophil respiratory burst and other antimicrobial functions to develop therapeutic strategies that reduce Salmonella’s fitness in the gut.

Salmonella infections are a threat to both human and animal health. Multi-drug resistant infections are increasing at a dramatic rate, making it important to design new, non-antimicrobial strategies to eliminate Salmonella from the gut. Work in our laboratory is testing host-targeted therapeutics that have the potential to prevent Salmonella invasion into epithelial cells. We hypothesize that prevention of invasion will reduce collateral damage to the gut wall and will reduce Salmonella growth in the gut. Ultimately, we hope to reduce Salmonella shedding, environmental contamination, and transmission between animals.