Molecular And Genetic Basis Of Colistin Resistance In Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Acinetobacter baumannii is a bacterium that causes hospital acquired infections which have become difficult to treat due to the bacteria developing resistance to most antibiotics in routine use. Colistin is now widely used as 'salvage' therapy in patients with these infections. Colistin resistance is currently low but is an emerging problem. As a first step in combating this problem this project will identify how this bacterium becomes resistant to colistin.
Characterisation Of A Type V Secretion In Escherichia Coli And Determining Its Role In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$73,195.00
Summary
Disease causing bacteria assemble secretion systems to assist with colonisation, persistence and destruction of host tissue. These systems have been categorised as Type I to Type VI. A comprehensive understanding of these secretion systems, is of paramount importance for a complete understanding of bacterial pathogenesis. We will investigate the role of a novel Type V secretion system conserved amongst many human pathogens.
Shigella Flexneri O Antigen Polysaccharides: Biosynthesis, Function In Virulence, And Interaction With IcsA/VirG
Funder
National Health and Medical Research Council
Funding Amount
$468,055.00
Summary
Shigella flexneri bacteria cause dysentery in millions of humans each year. The bacterium invades and replicates within the cells of the large intestine. Inside cells, S. flexneri is able to use the host cell's actin-based motility machinery to become motile within the cells, and this can be seen as F-actin comet tails extending from one end of the cell. Bacterial cell surface components residing in the outer membrane are important for the bacterium's ability to cause disease. Two of these compo ....Shigella flexneri bacteria cause dysentery in millions of humans each year. The bacterium invades and replicates within the cells of the large intestine. Inside cells, S. flexneri is able to use the host cell's actin-based motility machinery to become motile within the cells, and this can be seen as F-actin comet tails extending from one end of the cell. Bacterial cell surface components residing in the outer membrane are important for the bacterium's ability to cause disease. Two of these components (lipopolysaccharides (LPS) and their polysaccharide chains (O antigens), and IcsA-VirG protein)) are required for initiating actin polymerisation, and mutations affecting synthesis of these components reduce ability to cause disease. In previous studies we have found that O antigen and the synthesis and function of IcsA are interrelated. This project will study how the O antigens are synthesised and their chain length determined by the Wzz protein, and the Wzz structure in relation to its function will also be characterised. The role played by O antigen in intracellular motility will be studied to determine the mechanisms involved. Infection of cells and cell free extracts, antibodies, and an enzyme which specifically degrades the O antigen, will be used to study how O antigen affect the interaction between bacteria with human cell proteins. The relationship between O antigen and IcsA function will be studied using monoclonal antibodies raised to IcsA. The effect of LPS on the outer membrane protease IcsP will be investigated, as will the effect of LPS lipid A mutations on O antigen and virulence. These studies will contribute to a better understanding of the biosynthesis of an ubiquitous bacterial cell surface component (O antigen), its function as a virulence factor in bacterial interactions with host cells. This may lead to novel therapeutic strategies to prevent and control Shigellosis and other bacterial infections.Read moreRead less
Cell Surface Protein Antigens Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$339,634.00
Summary
Periodontitis is a bacterial-associated disease of the supporting structures of the teeth and can result in tooth loss. The disease is classified as a major public health problem with an enormous economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of periodontitis in adults. We have developed methods to rapidly identify all the surface protein antigens of P. gingivalis using mass spectrometry and then using recombinant DNA technology to expres ....Periodontitis is a bacterial-associated disease of the supporting structures of the teeth and can result in tooth loss. The disease is classified as a major public health problem with an enormous economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of periodontitis in adults. We have developed methods to rapidly identify all the surface protein antigens of P. gingivalis using mass spectrometry and then using recombinant DNA technology to express these recombinant antigens for testing in animal models of disease. The aim of this project is: (i) to rapidly identify cell surface protein antigens of P. gingivalis using novel techniques. (ii) prepare these antigens using recombinant DNA technology. (iii) use patient and healthy subject sera as well as animal antisera to screen the recombinant antigens for suitable candidates for an immunodiagnostic product and-or vaccine. (iv) test the recombinant antigens in animal models of disease in an approach to identify a candidate antigen for a vaccine. The expected outcomes of this research are that (i) we will develop techniques that can be used to characterise the cell surface antigens of any pathogenic bacterium. (ii) we will determine the organisation and the structure of the cell surface proteins of P. gingivalis. (iii) we will identify an abundant, unique and immunogenic protein of the P. gingivalis surface that will be a suitable candidate antigen for the development of a sensitive and specific immunodiagnostic. (iv) we will identify a cell surface antigen that when used as a vaccine in animals prevents disease caused by P. gingivalis.Read moreRead less
This research program aims to gain a detailed understanding of the organisation of the cell surface at the molecular level. The cell surface is organised into domains with distinct functions. Visualisation of these domains, identifying their important components, and understanding how they form and function will have huge importance for therapeutic strategies aimed at combatting the changes associated with cell transformation in cancer and in other human diseases such as muscular dystrophy.
Membrane Attachment And Components Of The Ca2+ -triggered Release Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$386,498.00
Summary
Understanding and harnessing the fundamental cellular process of secretion will provide a wealth of new approaches to addressing problems associated with aging & disorders that are major health care burdens (e.g. neurodegeneration & diabetes). Understanding the vesicle docked state, and the contributions of different molecular components to the release process provides for unique insights into the underlying molecular mechanisms, thereby enabling safe, targeted control of this critical process.