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.
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
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.
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
Acinetobacter Baumannii Virulence From A Regulatory Perspective: The Role Of Two Component Signal Transduction Systems
Funder
National Health and Medical Research Council
Funding Amount
$608,731.00
Summary
Acinetobacter baumannii is becoming a significant pathogen in the hospital and more recently in the community. It is very resistant to removal from surfaces and upon entering the host is almost impossible to treat with currently available antibiotics. It causes a wide range of disease states from wound infections and pneumonia to bacteraemia; little is known of this process. This research will increase our understanding of the disease process, providing possible treatment options in the future.
The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Te ....The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Team has demonstrated that the Team is at the forefront of research in this area. The novel antibiotics work by preventing bacteria sticking to surfaces and by preventing the bacteria from releasing toxins. The studies will concentrate on those bacteria that produce infections in the lungs (acute pneumonia), eyes (corneal infection), ear (middle ear disease), and abscesses.Read moreRead less
How The Intracellular Pathogen Coxiella Burnetii Manipulates Host Small GTPases To Facilitate Disease
Funder
National Health and Medical Research Council
Funding Amount
$534,510.00
Summary
This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is stable in the environment and few organisms are required to cause disease. Coxiella is able to manipulate human cells to replicate in a unique location within the cell but little is known about how they do this. Here we will study the host proteins that are important during infection and how Coxiella manipulates these factors to facilitate ....This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is stable in the environment and few organisms are required to cause disease. Coxiella is able to manipulate human cells to replicate in a unique location within the cell but little is known about how they do this. Here we will study the host proteins that are important during infection and how Coxiella manipulates these factors to facilitate intracellular replication.Read moreRead less
Defining Pathogenic Mechanisms Of Intracellular Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$494,691.00
Summary
This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is very stable in the environment and few organisms are required to cause disease. Coxiella is able to commandeer human cells to replicate in a specialized vacuole but little is understood about how they do this. We will examine the virulence factors of Coxiella and investigate how they allow the bacteria to replicate inside human cells.
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 Pathogenesis Of Infections Caused By Clostridium Sordellii.
Funder
National Health and Medical Research Council
Funding Amount
$400,232.00
Summary
The bacterium Clostridium sordellii causes necrosis and multiorgan failure with a very high mortality rate of 70% in infections of drug users, transplant and post-abortion patients, and 100% for post-partum patients. Little is known about how C. sordellii causes such devastating disease; treatment of these infections is currently ineffective. This project will make a major contribution to our understanding of how disease is caused and may lead to improved prevention and treatment stratetegies.