Host-Pathogen Interactions Research Group
Research Group Head
The focus of our research is to determine the mechanisms by which bacterial pathogens interact with their host, then use this information to understand the specific immune responses essential for fighting infections and maintaining immune homeostasis in the body.
Our overarching goals are to make discoveries on the fundamental mechanisms of immunity to infections and inform the future development of therapeutics for bacterial infections and dysregulated immune responses in inflammatory diseases.
The model pathogen that we use in our research is Salmonella enterica. These pathogens are able to colonise a wide range of human and animal hosts and in humans, they can cause disease ranging from gastroenteritis to systemic disease, depending on the serovar of the bacteria. S. enterica serovars Typhi and Paratyphi are human restricted and are known as the ‘Typhoidal’ Salmonella. These serovars cause serious illness as the bacteria disseminates systemically, causing severe fever, nausea, diarrhoea, abdominal cramping and headaches, and if left untreated, can cause death. Other non-typohoidal Salmonella serovars (NTS) include S. enterica serovars Typhimurium and Enteritidis, both of which account for the majority of gastrointestinal disease (salmonellosis) in immunocompetent individuals worldwide. In immunocompromised people however, some NTS strains cause invasive disease and thus more serious illness. S. enterica is endemic in many developing countries and is a constant major health concern in immunocompromised patients with HIV. Interestingly, Australia has one of the highest rates of salmonellosis among developed countries, with 74.6 and 67.9 cases per 100,000 people in 2016 and 2017, respectively.
In our lab, we aim to understand the virulence mechanisms of these pathogens and concurrently the host mechanisms that mediate protection against, or increased susceptibility to disease. We are particularly interested in programmed cell death signalling pathways, including apoptosis, necroptosis and pyroptosis during bacterial gut infection.
Given that we aim to characterise host innate immune signalling pathways that protect against bacterial gut infection, we also have a keen interest in whether these pathways play a role in maintaining homeostasis of the gut in general. What does this mean?
At any time, our gut is full of microbes, some that are relatively harmless and some that have pathogenic potential. How is it that we can generally tolerate all these microbes in our everyday lives? And why do some people develop serious inflammation in the bowel? We would like to know whether our work on pathogenic gut bacteria can provide insights into the specific immune signalling pathways that are most important in protecting against inflammation on an everyday basis. We are also interested in how mutations in these immune signalling pathways or serious gut infections may affect the composition of the gut microbiome, and what the long term implications of this may be in certain individuals.
- In vivo role of necroptosis in bacterial gut infection
- Regulation of TNFR signaling in Salmonella infection
- Characterisation of invasive non-typhoidal Salmonella lineages
- Inflammation and cell death in inflammatory bowel disease
- Bacterial and viral co-infection and potentiation of enteric disease
Pearson JS, Giogha C, Ong SY, Kennedy C, Kelly M, Robinson KR, Wong T, Mansell A, Riedmaier P, Oates CVL, Zaid A, Mühlen S, Crepin VF, Marches O, Ang C, Williamson NA, O’Reilly LA, Bankovacki A, Nachbur U, Infusini G, Webb AI, Silke J, Strasser A, Frankel G, Hartland, EL (2013) A type III effector antagonises death receptor signalling during bacterial gut infection. Nature 501:247-251.
Pearson JS*, Giogha C*, Mühlen S, Nachbur U, Wong Fok Lung T, Zhang Y, Oates C, Ingle D, Hildebrand J, Dagley L, Bankovacki A, Schroeder G, Frankel G, Masters S, Vince J, Webb A, Silke J, Hartland EL (2017) A bacterial cysteine protease effector cleaves RHIM proteins to block necroptosis and inflammation. Nature Microbiology (2017) 2:16258 *Joint first authors.
Creuzburg K, Giogha C, Wong Fok Lung T, Scott NE, Mühlen S, Hartland EL, Pearson JS (2017) The type III effector NleD from enteropathogenic coli differentiates between host substrates p38 and JNK. Infection and Immunity 85(2):e00620-16.
Wong Fok Lung T, Giogha C, Creuzburg K, Ong SY, Pollock G, Zhang Y, Fung KY, Pearson JS, Hartland EL (2016) Mutagenesis and functional analysis of the bacterial arginine glycosyltransferase effector NleB1 from enteropathogenic Escherichia coli. Infection and Immunity 84 (5), 1346-1360.
Pollock G, Oates C, Giogha C, Wong Fok Lung T, Ong SY, Pearson JS, Hartland EL (2017) Distinct roles of the anti-apoptotic effectors NleB and NleF from enteropathogenic Escherichia coli. Infection and Immunity 85(4) pii: e01071-16.