Research

Bacterial Signal Transduction Pathways

Monitoring a diverse array of intracellular and extracellular stimuli and promoting appropriate responses to these cues are vitally important for bacteria to thrive in different environments and conditions. Bacteria have evolved a wide range of signal transduction systems that are designed to specifically detect just one or sometimes a collection of stimuli at a wide range of concentrations. Each signal transduction system can initiate a simple or complex activation pathway that results in a change of transcription of specific genes that are beneficial for the bacterium to grow and survive in a defined condition.

One type of bacterial signal transduction system we have investigated is represented by the Campylobacter jejuni FlgSR two-component regulatory system. Many other polarly-flagellated bacteria such as Vibrio, Pseudomonas, and Helicobacter species contain a similar system that is required for expression of specific sets of flagellar genes necessary to construct a flagellum to promote swimming motility. We have explored the stimuli detected by this signal transduction system and how the system communicates the detection of the stimulus within the cell to promote expression of flagellar genes.

Signal transduction pathway mediated by the C. jejuni FlgSR two-component regulatory system and flagellar components.

From our analysis, we have found that the C. jejuni FlgSR system is an example of a signal transduction system that detects an intracellular stimulus – the formation of a regulatory checkpoint during flagellar biogenesis created by the flagellar type III secretion system, MS ring and rotor. These structures form the base of the flagellum that is largely required for secretion of most flagellar proteins that form the structural components of the flagellar motor. We are further dissecting this system in C. jejuni and other bacteria to understand the molecular interplay between the sensor, stimulus, and output components necessary for precise and proper expression of flagellar genes.

We also have a great interest in understanding how C. jejuni senses in vivo signals within the human or avian host. We suspect that these hosts harbor different stimuli that can be perceived by the bacterium. Appropriate expression of different types of genes in the human and avian hosts is vital for the ability of the bacterium to thrive in the hosts to result in the different outcomes of infection, such as diarrheal disease in humans and a persistent commensal colonization in chickens. We have identified a specific set of signals within avian hosts that likely allow C. jejuni to determine its spatial orientation within the avian intestinal tract to induce expression of factors necessary for colonization in different intestinal organs. We are pursuing how these signals are sensed in C. jejuni and the transcriptional mechanisms underlying the expression of specific genes.

Relevant Publications