Systems-level Characterisation And Therapeutic Targeting Of Small RNAs In Acinetobacter Baumannii Disease
Funder
National Health and Medical Research Council
Funding Amount
$581,990.00
Summary
This proposal aims to understand how a superbug that causes severe infections in hospitalised patients worldwide and is known to be resistant to almost all available antibiotics, causes disease. We then plan on using this information to guide the development of a new type of therapy to treat this severe infection.
Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.
Molecular Characterization Of E. Coli That Cause Urinary Tract Infection
Funder
National Health and Medical Research Council
Funding Amount
$387,114.00
Summary
The long term goals of the proposed research are to understand the processes by which uropathogenic Escherichia coli (UPEC) cause acute, recurrent and chronic infections and to identify new UPEC targets for therapeutic intervention. Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for more than 1 million hospitalizations and $1.6 billion in medical expenditures each year. It is estimated ....The long term goals of the proposed research are to understand the processes by which uropathogenic Escherichia coli (UPEC) cause acute, recurrent and chronic infections and to identify new UPEC targets for therapeutic intervention. Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for more than 1 million hospitalizations and $1.6 billion in medical expenditures each year. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime. The recurrence rate is high and no treatment other than antibiotics (often inefficient) is currently available. UPEC are the primary cause of UTI. In the last grant period, we focused on the molecular interplay that exists between different surface adhesins of UPEC. We succeeded in demonstrating functional interference between adhesins, motility organelles, aggregation factors and the capsule. We also discovered and partially characterized several novel UPEC adhesins that may play a role in pathogenesis. We established two novel technology sets: a mouse model of ascending UTI and the flow chamber biofilm model. In the next grant period, we will build on these concepts and experimental systems to gain a deeper understanding of the molecular mechanisms underlying UPEC virulence. We will characterize the role of several novel UPEC surface proteins in cell adhesin, aggregation, biofilm formation and colonization of the mouse urinary tract. We will employ an integrated approach that combines a powerful bacterial genetic system, a biofilm model, a mouse UTI model, microscopy and tissue culture systems to reveal the cellular, molecular, and structural basis for the pathogenesis of UTI. The work will facilitate the development of new vaccine approaches to prevent UTI, such as novel mechanisms for strain attenuation and vaccine design. The burden of UTI disease demands such research endeavours.Read moreRead less
Functional Genomics Of Malaria Liver Infection And Transmission
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Chemotherapy is the front line defense against malaria but resistance is emerging. The WHO has advised that new drugs should target parasite stages that perpetuate the transmission of malaria to break the cycle of infection. We have identified proteins that are essential for the two transmissive stages of the most deadly parasite to infect their hosts. We will determine the precise function of these proteins and the mechanisms they govern. This may guide the development of new interventions.
Role Of Plasmepsin V And PTEX Complex In Plasmodium Liver Infection
Funder
National Health and Medical Research Council
Funding Amount
$848,408.00
Summary
Plasmepsin V and PTEX are essential proteins for malaria parasites to grow inside red blood cells. These proteins control the export of parasite proteins into red cells, causing disease. Before red blood cells are infected, parasites invade liver cells. Plasmepsin V and PTEX are expressed during liver infection but their function is currently unknown. We hypothesise that they allow parasites to export proteins into liver cells in order to survive and, thus, are antimalarial drug targets.
Helicobacter Pylori Acquisition Of Host Cholesterol: Its Role In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$417,380.00
Summary
The bacterium Helicobacter pylori is present in the stomach of half the world’s population. It is estimated that 20% of these people will suffer from peptic ulcer disease, whereas as many as 1% will develop stomach cancer later in life. The common factor in all these diseases is the inflammation induced by the bacterium. This project will investigate a new mechanism by which H. pylori causes inflammation and how dietary cholesterol may be involved in this process.
Contribution Of Shigella And Escherichia Coli Pathogenicity Islands To Diarrhoeal Disease
Funder
National Health and Medical Research Council
Funding Amount
$303,677.00
Summary
Diarrhoea resulting from infection with Shigella and Escherichia coli is a major cause of sickness and death in the developing world, especially in children. Even in Australia, these bacteria, which may be food borne, are occasionally responsible for life threatening infections. In this study, we will investigate the contribution to diarrhoeal disease of large fragments of foreign DNA which have been recently acquired by these bacteria. We will characterise several of these elements in detail, i ....Diarrhoea resulting from infection with Shigella and Escherichia coli is a major cause of sickness and death in the developing world, especially in children. Even in Australia, these bacteria, which may be food borne, are occasionally responsible for life threatening infections. In this study, we will investigate the contribution to diarrhoeal disease of large fragments of foreign DNA which have been recently acquired by these bacteria. We will characterise several of these elements in detail, identifying novel virulence determinants and toxins in the process. We will also explore the means by which these packages of nasty DNA transfer between bacteria and investigate their potential to give rise to new, more virulent strains of bacteria. This study is particularly significant because it will lead to an improved understanding of how bacteria cause disease and may help to guide us in developing better strategies for the prevention of bacterial diarrhoea. Specifically, the work done on characterising large clusters of virulence genes will allow us to construct safer bacterial vaccines and we expect that in the future this knowledge will contribute to the development of new and better diagnostic and therapeutic agents against these harmful bacteria.Read moreRead less
Manipulation Of Clathrin-mediated Trafficking By Coxiella
Funder
National Health and Medical Research Council
Funding Amount
$667,857.00
Summary
This research will uncover how Coxiella causes the serious infectious disease Q fever by commandeering human cells and replicating to high numbers within a specialised vacuole. We will investigate virulence factors of Coxiella, learning how and why they target an essential human vesicular trafficking process. Our innovative approach and unique expertise will elucidate interaction between this pathogen and the human cell, providing fundamental knowledge towards public health outcomes.
Identification Of Type III Effectors In Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Salmonella is a major cause of disease across the world. In order to cause disease, Salmonella injects certain molecules into our own human cells to reprogramme them to promote Salmonella infection. This work aims to identify a large proportion of those molecules injected by Salmonella. Once identified, a more complete understanding of exactly how Salmonella reprogrammes our cells will be possible, enabling new avenues for therapeutics.
Functional Characterisation Of The SseK/NleB Family Of Type III Secreted Effectors In Salmonella And E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$510,183.00
Summary
Salmonella and E. coli cause enteritis and diarrhoea in a large proportion of the world's population including Australia. Certain strains of Salmonella also cause a more serious disease called typhoid fever. Together, diseases caused by Salmonella and E. coli are a major cause of illness and death. In order to cause disease Salmonella and E. coli use a specialised apparatus that functions like a needle and syringe to inject Salmonella proteins into human cells. These proteins that are injected i ....Salmonella and E. coli cause enteritis and diarrhoea in a large proportion of the world's population including Australia. Certain strains of Salmonella also cause a more serious disease called typhoid fever. Together, diseases caused by Salmonella and E. coli are a major cause of illness and death. In order to cause disease Salmonella and E. coli use a specialised apparatus that functions like a needle and syringe to inject Salmonella proteins into human cells. These proteins that are injected into human cells actively reprogram human cells to benefit the disease causing bacteria. We have recently discovered a new family of injected proteins and we aim to determine how these new proteins reprogram human cells and what this contributes to diarrhoea and typhoid fever. This information may lead to the development of more effective treatments for these important diseases.Read moreRead less