Bacterial Inhibition Of Cell Signalling And Apoptosis During Gastrintestinal Infection
Funder
National Health and Medical Research Council
Funding Amount
$542,011.00
Summary
E. coli are a major cause of severe diarrhoeal disease. In order to establish infection, E. coli inhibits a host response where cells with bacteria stuck to them are ‘killed off’ and excreted as waste. This recent discovery illuminated an unknown role for cell death in the immune response during bacterial gastroenteritis. This project will study this phenomenon further to better understand the host immune response to infection and also other gut diseases such as inflammatory bowel disease.
Randomised Controlled Trial Of The Use Of Nitazoxanide Versus Placebo To Treat Gastroenteritis Among Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$1,324,808.00
Summary
Better treatment strategies are needed for Indigenous children with gastroenteritis. At present, most treatment is supportive only, with little effect on the duration of symptoms. Nitazoxanide appears to have effects on a broad range of pathogens which cause gastroenteritis, but it is not clear whether it will be of benefit in this population. We will compare the speed of symptom resolution in children who receive nitazoxanide with a group who receive a placebo instead.
Host innate defence relies on the activation of several signalling pathways that regulate inflammation and cell death. Several important bacterial pathogens of humans inject virulence “effector” proteins into infected cells that interrupt host cell signalling pathways. We recently discovered a family of new effector proteins that directly degrade host proteins and block cell death. Here we will characterise this and other members of the family to understand their role during infection.
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.
Death Receptor Signaling During E. Coli And Salmonella Infection
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Upon encountering invading microorganisms, the body’s immune system usually initiates an inflammatory response to recruit populations of immune cells to the site of infection. To counter this attack, many bacterial pathogens have evolved distinct ways of disarming the inflammatory response. We are investigating the discovery that gastrointestinal bacteria such as Salmonella and pathogenic E. coli specifically interfere with the messages sent by the body’s innate sensors to recruit killer immune ....Upon encountering invading microorganisms, the body’s immune system usually initiates an inflammatory response to recruit populations of immune cells to the site of infection. To counter this attack, many bacterial pathogens have evolved distinct ways of disarming the inflammatory response. We are investigating the discovery that gastrointestinal bacteria such as Salmonella and pathogenic E. coli specifically interfere with the messages sent by the body’s innate sensors to recruit killer immune cells.Read moreRead less
Glycosyltransferase Effectors From Bacterial Enteric Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$772,600.00
Summary
Many disease-causing microbes subvert host cell defences to establish infection in part by transporting virulence proteins, termed “effector” proteins, into host cells via specialized protein secretion systems. We have discovered a new family of bacterial effectors that modify host proteins with a sugar and thereby inactivate them. Here we will characterise the function of these effector proteins during infection with E. coli and Salmonella.
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.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
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
Structural And Functional Analysis Of Glucosyltransferases (Gtr) Involved In O-antigen Modification Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$340,976.00
Summary
Shigellosis caused by Shigella flexneri is a medically significant disease in developing countries. Serotypes of S. flexneri are determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses carry the genes which confer O-antigen modification giving rise to different serotypes. The project will address fundamental processes related to the O-antigen modification by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster.