Translocated type III secretion system effectors of bacterial pathogens
Many bacterial pathogens have the ability to transport virulence proteins, termed effector proteins, into host cells via a specialised protein secretion system called a type III secretion system (T3SS). Elizabeth’s group works on a range of T3SS effectors from bacterial enteric pathogens, which interfere with host innate immune signalling pathways and block inflammation and cell death. The aim of their research is to identify the biochemical activity of T3SS effector proteins and understand their influence on host cell function, inflammatory signalling and the immune response.
Translocated Dot/Icm effectors of Legionella
Legionella pneumophila is an environmental organism and the major cause of Legionnaire’s Disease, an acute form of pneumonia. The Legionella genome encodes around 300 effector proteins that are translocated into eukaryotic cells by the Dot/Icm type IV secretion system (T4SS). The function of the vast majority of effectors is unknown. Many effectors share similarity with eukaryotic proteins and these are predicted to allow L. pneumophila to manipulate host cell processes by functional mimicry of eukaryotic proteins. Elizabeth’s group’s aim is to identify the biochemical function of Dot/Icm effector proteins, which will allow them to understand the molecular mechanisms by which Legionella replicates in the human lung and causes disease.
Immune responses in Legionnaire’s disease
Infection with L. pneumophila elicits a strong inflammatory response in the lung. This initial inflammation is important for subsequent recruitment and activation of immune responses necessary to control and clear the infection. Elizabeth’s group has discovered that certain subsets of dendritic cells (DC) play a role in limiting bacterial replication in the lung. The aim of this work is to understand the mechanisms by which DC contribute to resistance to infection with Legionella and other bacterial pathogens. This work will not only contribute to their understanding of the pathogenesis of Legionnaire’s disease, but will also provide novel information on the functions of DC in the lung.
Mucosal immune responses during bacterial diarrhoea
Susceptibility to gastrointestinal pathogens is the result of complex interplay between bacterial and host factors. Attaching and effacing pathogens interfere with inflammatory and cell death signalling to overcome the host response. At the same time, multiple immune receptors attempt to activate the host response. Elizabeth’s group has discovered that cell death pathways in particular play a critical role in clearing bacterial infection and eliciting a productive immune response. They are using mice deficient in certain cell death signalling proteins and a mouse-specific attaching and effacing pathogen to understand which host factors play a critical role in fighting bacterial diarrhoea.
Professor Elizabeth Hartland obtained her Bachelor of Science (Honours) majoring in microbiology and biochemistry, and subsequently her PhD in microbiology from the University of Melbourne. She has held a Royal Society/National Health and Medical Research Council (NHMRC) Howard Florey Fellowship in the Department of Biochemistry, Imperial College, London, UK and Lecturer/Senior Lecturer positions in the Department of Microbiology, Monash University. She was an inaugural Australian Research Council Future Fellow at the University of Melbourne and is currently Professor and Head of the Department of Microbiology and Immunology at the University of Melbourne and a Deputy Director of the Doherty Institute. She has a long-standing research interest in the pathogenesis of infections caused by Escherichia coli and Legionella, with a focus on mechanisms of bacterial colonisation and immune evasion.