A New Model For The Pathogenesis Of Rheumatic Fever: Superantigen Priming Of The Immune Response To Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$248,820.00
Summary
Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, c ....Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.Read moreRead less
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 Interactions With The Host In Gastrointestinal Infection And Disease
Funder
National Health and Medical Research Council
Funding Amount
$511,467.00
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.
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.
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.
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
Some of the world's most important diseases, including important diseases of indigenous chilren and the hospitalised elderly are caused by bacteria that carry a surface coating called a capsule. It is not clear how this capsule is retained by bacteria. Resolution of this question could lead to the development of new disinfectants that will stop hospital-acquired infections, to new reagents that can be incoporated into medical devices where bacteria frequently grow, and new antibiotics.
The Role Of Host Proteases In Modulating Enteric Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,267,155.00
Summary
Bacterial pathogens that cause gut diseases result in 2.5 million deaths per year. The gut is a complex environment consisting of numerous factors that must be balanced to maintain enteric health. When these factors are unbalanced, disease can occur, and infections can cause imbalances. This project will increase our understanding of the role that host proteins play in gut infections, providing knowledge critical for developing improved strategies for disease treatment and prevention.
Novel Therapeutic And Preventive Strategies For Clostridium Difficile Infections.
Funder
National Health and Medical Research Council
Funding Amount
$508,556.00
Summary
The bacterium Clostridium difficile is the major cause of nosocomial diarrhoea in many countries, including Australia. More virulent isolates have recently emerged, leading to increased incidence and disease severity in many countries. This project will make a major contribution to our understanding of how these bacteria cause disease. Preventive or treatment measures based on these research findings will help to prevent or lessen the severity of any epidemics that occur in Australia.
Is Mycobacterium Ulcerans A Zoonotic Agent Spread By Mosquitoes?
Funder
National Health and Medical Research Council
Funding Amount
$335,853.00
Summary
Last year record numbers of a mysterious flesh-eating bacterial disease called Buruli ulcer were reported in Australia. Wild animals such as possums and rats harbour the bacteria in their guts but we don't know how the disease is transmitted to humans. In this project we will work out how the bacteria survives in the guts of animals and how people contract Buruli ulcer. With this information we can stop the spread of this debilitating disease.