Investigation of Sensory Cyclic-di-GMP Phosphodiesterases in Salmonella

Additional Authors

N/A

Abstract

Salmonella enterica serovar Typhimurium infects humans and animals via consumption of contaminated food or water. Human infections with Salmonella typically lead to gastrointestinal disease but may also cause a systemic infection if it reaches the bloodstream where Salmonella is taken up by macrophages. After undergoing phagocytosis, Salmonella creates a vacuole inside of the macrophage allowing Salmonella to survive and continue to infect healthy cells. We want to study Salmonella’s adaptation inside macrophages to find out what signals are being used to trigger intracellular survival. Cyclic-di-GMP is one signaling system used by Salmonella to respond to its environment. External stimuli activate phosphodiesterases (PDEs) and diguanylate cyclases (DGCs) to degrade and synthesize cyclic-di-GMP respectively. Three PDEs were identified that work to degrade cyclic-di-GMP during intracellular survival and are required for full virulence. Two of these PDEs (STM2215 and STM2503) contain sensory domains that stimulate the dimerization required for activity. To monitor the response of these sensory domains to potential signals, we have modified a Bacterial Two-Hybrid system and Miller Assay to measure dimerization of PDEs when exposed to specific signals found inside of a macrophage. We are testing a wide range of potential signals that could be the source of intracellular stimuli to these PDEs. Our end goal is to see what type of signals STM2215 and STM2503 respond to once inside of a macrophage that promotes Salmonella survival in the midst of phagocytosis.

Start Time

16-4-2025 10:00 AM

End Time

16-4-2025 11:00 AM

Room Number

303

Presentation Type

Oral Presentation

Presentation Subtype

Grad/Comp Orals

Presentation Category

Science, Technology and Engineering

Faculty Mentor

Erik Peterson

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Apr 16th, 10:00 AM Apr 16th, 11:00 AM

Investigation of Sensory Cyclic-di-GMP Phosphodiesterases in Salmonella

303

Salmonella enterica serovar Typhimurium infects humans and animals via consumption of contaminated food or water. Human infections with Salmonella typically lead to gastrointestinal disease but may also cause a systemic infection if it reaches the bloodstream where Salmonella is taken up by macrophages. After undergoing phagocytosis, Salmonella creates a vacuole inside of the macrophage allowing Salmonella to survive and continue to infect healthy cells. We want to study Salmonella’s adaptation inside macrophages to find out what signals are being used to trigger intracellular survival. Cyclic-di-GMP is one signaling system used by Salmonella to respond to its environment. External stimuli activate phosphodiesterases (PDEs) and diguanylate cyclases (DGCs) to degrade and synthesize cyclic-di-GMP respectively. Three PDEs were identified that work to degrade cyclic-di-GMP during intracellular survival and are required for full virulence. Two of these PDEs (STM2215 and STM2503) contain sensory domains that stimulate the dimerization required for activity. To monitor the response of these sensory domains to potential signals, we have modified a Bacterial Two-Hybrid system and Miller Assay to measure dimerization of PDEs when exposed to specific signals found inside of a macrophage. We are testing a wide range of potential signals that could be the source of intracellular stimuli to these PDEs. Our end goal is to see what type of signals STM2215 and STM2503 respond to once inside of a macrophage that promotes Salmonella survival in the midst of phagocytosis.