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
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.
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.
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
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.
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.
Pathogenic Consequences And Mechanistic Insights Of Daptomycin Resistance In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$540,633.00
Summary
Staphylococcus aureus is one of the most common human bacterial pathogens. This project aims to characterise the mechanisms that Staph uses to develop resistance to one of our last-line antibiotics, and will determine the effects of this resistance on the ability of the bacteria to cause human disease.
Improving Prevention, Tracking And Treatment Of Major Human Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$467,961.00
Summary
This research fellowship will lead to a detailed understanding of the mechanisms by which bacteria become resistant to antibiotics and cause diseases, how bacterial pathogens evolve and spread in the Australian community, and will result in new understanding of the optimal treatment of bacterial diseases and identification of compounds for new antibiotic development.