Black Death Genomics And The Evolution Of Pathogen Virulence
Funder
National Health and Medical Research Council
Funding Amount
$525,412.00
Summary
The Black Death was one of the most lethal plagues of antiquity and changed the course of human history. We will reconstruct and analyse the evolution of its causative agent – the bacterium Yersinia pestis – sampled from human skeletal remains dating back to the Black Death and beyond. We will determine the mutations that changed the virulence of plague epidemics through time, enabling a unique insight into the most dramatic example of pathogen emergence that has ever been available for study.
Expression And Secretion Of Large Clostridial Toxins From The Pathogenic Clostridia.
Funder
National Health and Medical Research Council
Funding Amount
$332,258.00
Summary
The large clostridial toxins are an important family of bacterial virulence factors that includes toxins from many disease-causing clostridial species. Despite their impact on public health, pathogenesis of disease caused by these bacteria is poorly understood. We will analyse how these bacteria regulate the production and secretion of the large toxins, which will give us a better understanding of the mechanisms of disease causation as well as identifying novel common therapeutic targets.
Non-coding RNA Regulation Of Virulence In Enterohaemorrhagic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$389,313.00
Summary
Shiga toxins cause potentially fatal haemolytic uremic syndrome (HUS) and are transferred between bacterial pathogens by bacteriophage (bacterial viruses). We have recently found that the Shiga toxin encoding bacteriophage encodes an unusually large number of non-coding RNAs (RNA regulators of gene expression). This Project aims to understand how these RNA regulators benefit the Shiga toxin bacteriophage and use this knowledge to develop interventions that will prevent expression of the toxin.
Role Of Autotransporter Proteins In Uropathogenic E. Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$611,149.00
Summary
Urinary tract infections (UTI) are among the most common infectious diseases of humans. Uropathogenic E. coli (UPEC), the primary cause of UTI, utilize a range of adherence mechanisms to colonize the urinary tract. In this project we will characterise the function and mode of secretion for one important class of UPEC adherence factors – autotransporter proteins. This work may inform new approaches to prevent UTI, an urgent need given the rapid increase in resistance to antibiotics among UPEC.
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.
Bacterial And Host Drivers Of Fulminant Community-acquired Acinetobacter Baumannii Infection
Funder
National Health and Medical Research Council
Funding Amount
$729,315.00
Summary
This proposal aims to understand how a bacterial pathogen causes severe, life-threatening infections in people from the community in northern Australia. This severe infection particularly impacts people who drink excess alcohol or have diabetes mellitus, and importantly impacts Indigenous Australians the greatest. This work will provide, for the first time, important insights into new prevention and treatment strategies for a serious infection impacting Australians and those in our region.
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.
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.
Role Of Streptococcus Agalactiae Glyceraldehyde 3-phosphate Dehydrogenase (GAPDH) In Infection And Potential As A Target To Control Colonization In The Female Genital Tract
Funder
National Health and Medical Research Council
Funding Amount
$677,177.00
Summary
Extracellular proteins produced by pathogenic bacteria can facilitate microbial colonization of the host by mediating binding to host cells and by modulating the immune system. These proteins exert their effects by subverting specific elements of the immune system and this can allow infection to worsen. This project will increase our understanding of how this bacterium chronically colonizes humans and will identify the potential of a bacterial protein, termed GAPDH, as a target for control.
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.