Diabolic Regulation Of Macrophage Cell Death Pathways By Legionella
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
The bacterial pathogen Legionella causes fatal pneumonia in immuno-compromised humans. Infections depend on a sophisticated secretion machinery that translocates hundreds of proteins into host cells. These proteins subvert several essential defense pathways, including cell death signals. This project will highlight how Legionella interfere with cell death pathways and control the survival of its host cells. These findings will facilitate the development of promising new anti-bacterial agents.
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
Characterization Of A Novel Secretion And Attachment System Necessary For The Formation Of A Virulence Coat In Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$828,857.00
Summary
In this study we will characterize a novel bacterial secretion system that we have discovered. This system mediates the secretion of proteins from the bacterial cell and their attachment to the cell surface. This system is essential for the virulence of a bacterium associated with severe gum disease. The chacterization of this system may offer opportunities for the development of new treatments to target this disease.
The Role Of N-linked Protein Glycosylation In Campylobacter Jejuni Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$757,600.00
Summary
Protein glycosylation is crucial in enabling C. jejuni to colonize poultry, which is the most common route to human infection. The roles played by this modification remain almost completely unknown yet are likely to be multi-factorial. This project will determine the function of glycosylation and thus lead to eventual interventions aimed at reducing the organism in poultry for human consumption.
Mechanisms Of Immune-evasion By Group A Streptococcus During Skin Infection
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Infections by Group A Streptococcus (GAS), or Streptococcus pyogenes, represent a global health concern. Currently no vaccine exists against GAS thereby mandating a better understanding of the immune response against the bacterium. Using in vivo microscopy, the aim of this proposal is to dissect in real time how neutrophils detect and destroy GAS following skin infection, and how the bacterium manages to circumvent the attack by innate immune cells.