Evolution And Function Of A Novel Lateral Flagellar Locus, Flag-2, In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$465,158.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified a novel genetic region that allows E. coli to survive and persist in the intestine. Similar genes are also present in closely related organisms. This project will help us to undestand how new diseases evolve and emerge and may lead to the development of new vaccines to protect against infant diarrhoea.
The Intracellular Replicative Niche Of Legionella Species And Coxiella Burnetii.
Funder
National Health and Medical Research Council
Funding Amount
$529,632.00
Summary
This project will study how the bacterium that causes Legionnaire's disease survives and grows inside human cells. We have identified new bacterial proteins that allow Legionella to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Coxiella, which causes Q-fever. By determining how these proteins act, this work may result in new treatments for Legionnaire's disease and related infections.
The Role Of Actin-based Motility As A Virulence Mechanism And Potential As An Antiviral Target
Funder
National Health and Medical Research Council
Funding Amount
$325,798.00
Summary
Our repertoire of effective treatments for infectious diseases is fast becoming exhausted as resistance to antibiotics and antivirals evolves and rapidly spreads throughout our community. We have developed a new paradigm in treating viral diseases that we predict will not give rise to resistance, and this project will be the first to demonstrate the effectiveness of this novel therapy in an endemic disease model.
Structural Characterization Of Novel AB5 Cytotoxin - SubAB
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
AB5 toxins are virulence factors from a range of pathogenic bacteria, including Shiga toxigenic E. coli (STEC), S. dysenteriae, V. cholerae, and B. pertussis. AB5 toxins comprise a catalytic A subunit that disrupts distinct essential cellular processes within the cell and a receptor binding, pentameric B subunit that enables the toxin to target certain cell types. We are structural characterizing a novel AB5 toxin that targets an essential component of the cellular machinery.
Functions Of Viral Chemokine Receptor Homologues Important For Cytomegalovirus Pathogenesis And Latency
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Cytomegalovirus (CMV) causes life-threatening disease in babies, transplant recipients and HIV-AIDS patients. We will focus on a CMV gene that has been 'hijacked' from the host cell and enables the virus to switch on signalling molecules within infected cells. We will determine how these signals enable CMV to infect sites of the body that are critical for virus transmission and contribute to long-term virus persistence. Our results will provide new strategies for drugs against CMV.
The Role Of The Intracellular Pathogen-recognition Molecule Nod1 In The Host Response To Helicobacter Pylori Infection.
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
The report in 1982 by two Australian clinicians, Drs Marshall and Warren, of a link between a spiral-shaped bacterium, Helicobacter pylori, and stomach disease in humans was to prove one of the ground breaking discoveries of medical research in the last 20-30 years. Despite extensive studies since, including the sequencing of the entire genomes of two different H. pylori isolates, many issues relating to H. pylori disease remain unanswered. For instance, it is still not known why all infected in ....The report in 1982 by two Australian clinicians, Drs Marshall and Warren, of a link between a spiral-shaped bacterium, Helicobacter pylori, and stomach disease in humans was to prove one of the ground breaking discoveries of medical research in the last 20-30 years. Despite extensive studies since, including the sequencing of the entire genomes of two different H. pylori isolates, many issues relating to H. pylori disease remain unanswered. For instance, it is still not known why all infected individuals develop inflammation of the stomach lining, yet only a proportion (15-20%) will go on to develop severe diseases, such as peptic ulcer disease and stomach cancer. Recent work from our groups has identified the mechanism by which H. pylori induces host responses in the cells lining the stomach, the epithelial cell. The interaction of the bacterium with these cells represents its first contact with the host, and sets the scene for the development of immune responses in the stomach. From their position on the outside surfaces of epithelial cells, certain strains of H. pylori are able to deliver a bacterial component into host cells, thus triggering an inflammatory response in the latter. Curiously, a host molecule called Nod1, which is present on the inside of cells and not on the surface, acts as an internal sensor by interpreting the entry of this H. pylori component as a danger signal for the host. The aim of the project will be to characterise the resulting defence mechanisms that are induced by Nod1 in order to prevent the colonisation of the stomach by H. pylori bacteria. It is expected that this work will address questions concerning the role of host immune defence mechanisms in H. pylori infection and stomach disease. Amongst the possible public health benefits of this work will be the development of novel therapies to reduce inflammation in the stomach by blocking Nod1 responses to H. pylori bacterial components.Read moreRead less
Determination Of The Mechanisms Of Action Of A Cytomegalovirus Chemokine Receptor Homologue In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$251,341.00
Summary
A number of herpesviruses encode proteins that are similar to proteins of our immune system. These pirated proteins are exploited by the virus to enable it to replicate and persist in the infected individual, usually by evading or gaining advantage from the normal immune response. This project will investigate the role of one such protein found in both human and animal herpesviruses (specifically cytomegaloviruses (CMV)) that is conserved with cellular cell surface proteins (receptors) that bind ....A number of herpesviruses encode proteins that are similar to proteins of our immune system. These pirated proteins are exploited by the virus to enable it to replicate and persist in the infected individual, usually by evading or gaining advantage from the normal immune response. This project will investigate the role of one such protein found in both human and animal herpesviruses (specifically cytomegaloviruses (CMV)) that is conserved with cellular cell surface proteins (receptors) that bind immune signaling molecules (chemokines). Chemokines are important proteins in the early response to infection. Binding of chemokines to their receptors initiates a cascade of signals within the cell that has profound effects on cellular responses to environmental stimuli. Thus, it is believed that herpesviruses have acquired chemokine receptors to modify or react to the immune response, causing infected cells to behave abnormally either despite or in response to chemokine signals. This project will determine how this CMV specific protein affects the function of cells that CMV infects and how this may promote virus replication, dissemination and persistence in infected hosts. We will also engineer CMVs where the activity of the target protein can be inhibited by administration of prototype antiviral drugs. If inhibition of the activity of the protein is found to reduce virus replication, dissemination or persistence, then this will demonstrate that this type of protein would be a suitable target for the development of novel drugs active against CMV infections. CMV can cause serious (potentially life threatening) disease in newborn children (following infection in the uterus) and immunosuppressed people (eg. organ transplant recipients and people with HIV-AIDS). Our studies will improve our understanding of the contribution of a specific CMV protein to disease, thereby assisting efforts to reduce the impact of CMV infections.Read moreRead less
Bacterial Outer Membrane Vesicles As Immunomodulatory Agents In Helicobacter Pylori Infection
Funder
National Health and Medical Research Council
Funding Amount
$306,510.00
Summary
Chronic inflammation of the stomach is a hallmark of Helicobacter pylori infection, and is a precursor to peptic ulcer disease and cancer. Like many other bacteria, H. pylori sheds spherical blebs from its surface. These blebs bind to stomach cells in vitro and have been found in stomach biopsies of H. pylori-infected subjects. The aims of the work are to investigate the mechanisms whereby H. pylori blebs enter and disseminate within host cells, and how this may contribute to inflammation.
Contribution Of Nuclear Targeting Of The NleE-OspZ Family Of Proteins To Escherichia Coli And Shigella Virulence
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified new bacterial proteins that allow E. coli to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Shigella which causes dysentary. We will determine how these proteins act by finding the host cell proteins they bind.
Characterisation Of Enterohaemorrhagic Escherichia Coli Lacking Classical Virulence Markers
Funder
National Health and Medical Research Council
Funding Amount
$140,660.00
Summary
Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this ty ....Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this type of E.coli and usually acquire the infection by consuming contaminated food or water. This organism is currently a global food safety problem and the bacteria are especially prevalent in ground beef products and water or vegetables that have been contaminated with cattle faeces. In this study we aim to identify new bacterial genes and proteins that may be used to improve current means of detecting and diagnosing this kind of E.coli. A great deal is known about the way in which the classical strains of this virulent E .coli colonise the intestine however a small but significant group of these organisms do not carry known colonisation factors. We aim to identify bacterial proteins in these non-classical strains of E.coli which are needed for attachment of the bacteria to the host. Identifying how these bacteria interact with the host may help us to develop improved means of detecting and diagnosing this life-threatening infection.Read moreRead less