A Novel Therapeutic Target For Preventing Helicobacter Pylori-associated Diseases
Funder
National Health and Medical Research Council
Funding Amount
$750,336.00
Summary
Gastric cancer mainly results from chronic inflammation (gastritis) caused by the stomach-dwelling bacterium, Helicobacter pylori. We have identified a potassium channel which our data suggest could be a new therapeutic target for protecting against gastric cancer caused by H. pylori infection. This project will test the role of this channel in H. pylori gastritis and see whether drugs that target this channel can protect mice against H. pylori-associated disease.
E. coli is a normal inhabitant of the human intestine, but some varieties can cause serious infections that may lead to the premature death of children, especially in less developed countries. The aims of this study are to learn more about these harmful varieties of E. coli and to enhance our ability to detect them in samples from patients and the environment.
Anti-sporulation Strategies For Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$651,559.00
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 strains have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains spread and will provide knowledge that is critical for developing improved strategies for preventing these infections.
Combating E. Coli Diarrhoea By Disarming Bacterial Virulence
Funder
National Health and Medical Research Council
Funding Amount
$674,737.00
Summary
E. coli causes severe and persistent diarrhoea which affects the health of millions of people worldwide. Although antibiotics may alleviate E. coli diarrhoea, these bacteria are becoming resistant to most drugs. In this study, we will use state-of-the-art technology to discover novel types of drug that treat and prevent infection with E. coli, without harming the beneficial bacteria in the gut.
Class-specific Virulence Determinants Of Atypical Enteropathogeneic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$672,134.00
Summary
Some varieties of E. coli cause diarrhoea, but they are difficult to diagnose in the laboratory. The aim of this study is to find specific genes of disease-associated E. coli that could be used as targets to identify these bacteria in patients with diarrhoea. The discovery of genes from E. coli that could be used as diagnostic targets will provide invaluable tools to study the epidemiology and clinical impact of these bacteria in patients in Australia and overseas.
Structure And Functional Characterisation Of AB5 Toxins
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
The proposed research program, using a combination of structure and biochemical analyses, will provide insight into two novel AB5 toxins that represent a medically important family of proteins. This study will not only improve our fundamental understanding of AB5 toxins action but could lead to rational design of antimicrobials.
Novel Antimicrobials That Target Enteropathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$617,525.00
Summary
Enteropathogenic E. coli (EPEC) cause acute and persistent diarrhoea which affect the health of millions of children each year. In this study, we will use the state-of-the-art-technology to identify small synthetic-compounds that inhibit the virulence of EPEC without affecting normal microflora. Molecular, cellular and animal tests of the compounds will be carried out to determine whether they can be used to treat gastrointestinal infection by EPEC.
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
Host Cell Death Signaling And Susceptibility To Bacterial Gut Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,321.00
Summary
Bacterial infections are a major cause of infectious disease worldwide. Here we aim to characterise immune responses that help fight infection by E. coli and Salmonella. These bacteria have evolved ways to shut down many of our immune responses during infection, allowing them to survive and cause disease. This work will help understand the complex relationship between gut bacteria and our immune system and provide solutions for controlling infection and treating immune disorders of the gut.
Iron, Pseudomonas Aeruginosa And Lung Disease In Cystic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$322,875.00
Summary
Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to inc ....Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to increase the understanding of how P. aeruginosa persists in the CF lung, with the goal of developing more effective therapeutic strategies to eliminate chronic infection with this bacterium. The new perception is that P. aeruginosa bacteria flourish in mucus with a low oxygen content within the CF lung and persist despite aggressive antibiotic therapy because they have adopted an antibiotic-resistant, biofilm mode of growth. This has opened up exciting directions for new therapeutic strategies. Factors in CF mucus that regulate this mode of bacterial growth are potential targets for intervention. Our past work has shown that iron is likely to be one such factor. In this study, we will extend these findings and determine whether using iron-binding chemicals can disrupt these biofims and allow the host immune system and antibiotics to work more efficiently to kill the bacteria. Not only will this study provide further insights into the pathogenesis of P. aeruginosa in CF and the role of iron, but ultimately it will contribute to the improved treatment and prevention of chronic infection with this organism.Read moreRead less