Salmonella Pathogenesis
Investigators
Salmonella species are extremely diverse pathogens capable of infecting reptiles, birds, cows and pigs and, of course, humans. Chances are everyone is familiar with the physiological effects of a Salmonella infection. In North America, these infections are usually self-limiting gastroenteritis coinciding with several days off work - which actually has a huge economic cost. In other areas of the world, such as developing countries, Salmonella infections can be more serious with severe dehydration combined with pre-existing health conditions (malnutrition, HIV infection) often leading to death.
My research program focuses on understanding the infectious process of Salmonella, particularly the transmission between hosts. For the past 10 years, I have studied an aggregative colony state termed the rdar morphotype that is conserved among the majority of disease-causing isolates. During rdar formation, cells produce a resistant extracellular matrix that serves as a protective niche. The aggregative protein polymers (fimbriae) and carbohydrate polymers (cellulose, capsules) in the matrix provide functions such as nutrient trapping, buffering and water retention. We have demonstrated that rdar provides a survival advantage for cells during desiccation and exposure to disinfectants. We hypothesize that the rdar morphotype represents an environmental survival phenotype that is critical for transmission between hosts.
The rdar state in Salmonella also serves as an effective model for biofilm formation. This is important given that the majority of bacterial life in nature is thought to exist in biofilms - there are many biofilm-related diseases of livestock as well as several human pathogens (i.e., E. coli, Listeria, Vibrio, Pseudomonas) that have "biofilm-like" modes of growth. Thus, the results of our studies could have broad implications for understanding survival and transmission of pathogens.
Goals and Objectives
The Long-term Goal of my research is to identify key control points that can be targeted to reduce or prevent environmental persistence and transmission of human pathogens.
The specific objectives include:
- Characterize the metabolic and genetic adaptations in Salmonella Typhimurium as cells aggregate to form biofilms and prepare for long-term survival and persistence in the environment.
- Screening and testing of new antimicrobial agents to act as biofilm "disrupters".
- Exploring the dynamics of transmission of S. Typhimurium from infected to non-infected mice.
- Identify new strategies to reduce or block transmission of Salmonella between animals.
- Designing vaccines targeted against components of the Salmonella extracellular matrix.
Graduate students will be exposed to both basic and applied research in a dynamic learning environment employing new technologies such as in vivo bioluminescence imaging and next generation sequencing.
