Dr Jaclyn PearsonHead of the Host-Pathogen Interactions Research Group, Hudson Institute of Medical Research
Decades of international research on bacterial gut pathogens has provided clinical and research communities with fundamental information on disease mechanisms of organisms such as Salmonella, Shigella, Yersinia and pathogenic E. coli. Yet despite the many years of intensive research efforts, hundreds of thousands of people still die each year from bacterial diarrhoea.
This highlights the need for a more complete understanding of the pathogenic mechanisms of these organisms, as well as a thorough understanding of host immune responses to infection, in order to develop effective vaccines and therapeutics for bacterial diarrhoea. The common theme among these bacterial gut pathogens is that they utilise a type III secretion system to inject bacterial virulence (effector) proteins directly into host cells which are essential for colonisation, evasion of host immune responses and subsequent disease.
Over the last eight years, our research team has made a number of significant discoveries on the mechanisms of type III effector proteins, many of which mediate highly novel biochemical modifications of host immune signaling proteins. Effector targets we have identified include NF-κB and MAPK signaling proteins as well as key mediators of extrinsic apoptosis such as FADD and RIPK1.
In addition, we have utilised these pathogens to interrogate dysregulation of host inflammatory and cell death processes in the gut during infection in vivo.
Overall, these findings have contributed significantly to our understanding of how bacterial gut pathogens modulate host innate immune responses during infection in order to persist in the host and cause disease, and also provided insights into inflammatory diseases of the gut, including Crohn’s Disease and Ulcerative Colitis.