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.
The Impact Of Clostridium Difficile Infection And The Host Immune Response On Colonic Homeostasis And Regeneration.
Funder
National Health and Medical Research Council
Funding Amount
$932,212.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains cause severe gut disease, which is critical for the development of improved strategies for preventing and treating these infections and reducing antibiotic use.
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.
The Role Of Clostridium Difficile Spore Surface Structures In Initiating Gastrointestinal Infection And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$467,556.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infection ....Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infections.Read moreRead less
Evolution And Pathogenicity Of NDM-1 Positive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$643,275.00
Summary
Antibiotic resistance (AR), as highlighted by the WHO, is the most pressing medical need of the 21C – some infections are now untreatable. Our research will focus on the new "superbug" NDM-1 positive E. coli. We will correlate AR and pathogenicity and explore the evolution of these "superbugs" using state-of-the-art sequencing. This research will benefit Australian medicine by predicting timelines of AR epidemics and by conducting the first analyses on the virulence potential of these strains.
Targeting Glycointeractions To Generate New Opportunities To Treat And Prevent Bacterial Infections.
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Bacteria and bacterial toxins can interact with complex sugar structures on human cells called glycans. My research team has identified new and important glycan interactions used by bacteria that cause diseases ranging from pneumonia, meningitis and food borne infections to urinary tract and sexually transmitted diseases. Now that these interactions have been discovered, they can be exploited to create drugs and vaccines that may treat and prevent disease by blocking the glycan interactions.
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
Virulence Associated Small RNAs In Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$964,148.00
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.
Integrated Bacterial Genomics And Virulence Analysis Of Uropathogenic Streptococcus Agalactiae
Funder
National Health and Medical Research Council
Funding Amount
$747,457.00
Summary
Urinary tract infections (UTI), which start as a bladder infection and often evolve to encompass the kidneys, are among the most common infectious diseases in humans. Streptococcus agalactiae is an important cause of gram-positive bacterial UTI. We will study the genomes and functions of specific genes in reference strains of this bacterium isolated from patients with different forms of infection to elucidate how bacterial genes and virulence factors contribute to these types of infections.
The Role Of Clostridium Difficile Virulence Factors In Mediating The Host-pathogen Interactions That Lead To Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains cause disease and why they are more harmful, which is critical for the development of improved strategies for preventing and treating these infections.