Structural Studies On The Conjugative Apparatus Of The Gram-positive Bacteria, Clostridium Perfringens.
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
Antibiotic resistance is a worldwide health problem. It has severely reduced the effectiveness of many antibiotics driving up the health care costs and death rates associated with bacterial infections. This project aims to investigate how antibiotic resistance determinants are transferred in the pathogenic bacteria, Clostridium perfringens. By understanding the mechanism of antibiotic resistance transfer in bacteria we will be better armed to combat antibiotic resistance.
The Mechanism Of Conjugative Transfer Of Antibiotic Resistance Genes In Gram Positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
Antibiotic resistant bacteria pose a serious threat to the health of Australians. We will determine how antibiotic resistance genes spread from one bacterium to another. Using a disease-causing bacterium as model we will determine the mechanism by which this gene transfer process occurs and the structure and function of the key components. The result will be major advances in our understanding of the evolution of the antibiotic resistant bacteria that are major causes of human disease.
Global Regulatory Networks That Control Virulence In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$531,557.00
Summary
This research focuses on the bacterium that is responsible for clostridial myonecrosis, or gas gangrene, an often fatal human infection. The objective is to determine how this bacterium controls the production of the various factors that are required to cause disease. The aims will be achieved by the integrated application of the latest techniques in microbiology and molecular biology and will result in a significant advancement in our knowledge of this complex regulatory process.
Regulation Of Virulence Gene Expression In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
This project involves the analysis of a bacterium that causes gas gangrene. We have shown that a previously unknown regulatory protein modulates the ability of this bacterium to cause disease. We aim to determine what turns on the protein's activity, how it controls the factors that contribute towards disease and what specific factors are involved in disease. The major outcome will be a better understanding of the mechanisms of virulence gene regulation, which will lead to improved methods of di ....This project involves the analysis of a bacterium that causes gas gangrene. We have shown that a previously unknown regulatory protein modulates the ability of this bacterium to cause disease. We aim to determine what turns on the protein's activity, how it controls the factors that contribute towards disease and what specific factors are involved in disease. The major outcome will be a better understanding of the mechanisms of virulence gene regulation, which will lead to improved methods of disease control.Read moreRead less
The aim of this project is to provide a better understanding of the mechanisms underlying the development of gas gangrene, an often fatal disease of particular significance to elderly and diabetic patients, who are particularly susceptible following injury, or surgery, or in some cases when suffering from colon cancer. Although research has been carried out on this disease for many years prompt surgical removal of the infected tissue, often including amputation of a limb, is still commonly used ....The aim of this project is to provide a better understanding of the mechanisms underlying the development of gas gangrene, an often fatal disease of particular significance to elderly and diabetic patients, who are particularly susceptible following injury, or surgery, or in some cases when suffering from colon cancer. Although research has been carried out on this disease for many years prompt surgical removal of the infected tissue, often including amputation of a limb, is still commonly used to ensure the patient's survival. This project involves the study of the two bacteria that are the major causes of the disease. We aim to find out how the bacteria mediate the disease, in particular to determine which toxic factors produced by the bacteria are involved. The normal host response to a bacterial infection is a rapid influx of white blood cells to the infected tissue, which is part of the normal inflammatory response. These cells engulf and degrade the bacteria, clearing the infection. However, a major characteristic of gas gangrene pathology is that very few white blood cells infiltrate the infected tissue. We aim to determine why the host fails to mount an inflammatory response to this bacterial infection. We will achieve this objective by developing a better understanding of the role of the bacterial toxins in the development of this morbid disease. It is hoped the results from this study will enable the development of more effective therapeutic and prophylactic treatments for this disease and also provide a foundation for studies into the modulation of the host response by other bacterial species.Read moreRead less
Global Regulation Of Toxin Production In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$389,860.00
Summary
This project involves an investigation of how the bacteria that cause an often fatal wound infection control the production of the toxic proteins that are essential elements of the disease process. In all pathogenic bacteria there are specific genes that encode the virulence factors that are involved in the disease. The expression of these genes is generally controlled by the products of other genes known as regulatory genes. The function of these regulatory networks is generally responsive to e ....This project involves an investigation of how the bacteria that cause an often fatal wound infection control the production of the toxic proteins that are essential elements of the disease process. In all pathogenic bacteria there are specific genes that encode the virulence factors that are involved in the disease. The expression of these genes is generally controlled by the products of other genes known as regulatory genes. The function of these regulatory networks is generally responsive to environmental stimuli. This project involves the detailed functional analysis of a regulatory network that was first identified in this laboratory and which controls the expression of extracellular toxins that have been implicated in gas gangrene. The overall objectives of the project are to develop a detailed understanding of the mechanisms involved in this regulatory process. Specifically, the project aims to determine the functional components of the regulatory proteins that interact with the environmental signal or which bind to the genes encoding the bacterial toxins, to determine the nature of the target sites to which the regulatory proteins bind, and to examine the hypothesis that there is another regulatory gene that is involved in this process. The project will make a major contribution to our knowledge of the complex interactions that occur between an invading bacterium and the host tissues. If we are to fully comprehend how bacteria cause disease then it is critical that we understand how bacteria control the production of the toxic products that are an integral part of the disease process.Read moreRead less
Host-pathogen Interactions In Clostridial Myonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$577,573.00
Summary
We will analyse the interaction between the bacteria that cause gas gangrene, and the infected host, from both a host and pathogen perspective. We will examine how the host’s response to infection can be modulated to decrease the severity of disease and we will identify the biochemical processes that are essential for bacterial growth in the host, a necessary prerequisite for disease. Outcomes will be a better understanding of the mechanisms of disease causation and improved disease control.
Two-component Regulatory Systems Involved In Toxin Production In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$78,500.00
Summary
The bacterium studied in this project causes gas gangrene, a severe and often fatal infection of traumatic or surgical wounds. The project involves the detailed analysis of the process by which this bacterium controls the production of the toxic proteins that are required for disease to occur. The emphasis is to determine the mechanism by which this regulatory process is mediated. Research in this laboratory has identified two genes whose protein products are the key links in this regulatory net ....The bacterium studied in this project causes gas gangrene, a severe and often fatal infection of traumatic or surgical wounds. The project involves the detailed analysis of the process by which this bacterium controls the production of the toxic proteins that are required for disease to occur. The emphasis is to determine the mechanism by which this regulatory process is mediated. Research in this laboratory has identified two genes whose protein products are the key links in this regulatory network. The objectives of the project will be to determine which part of the regulatory protein interacts with the target toxin gene, to start to determine the structure of the regulatory protein so that the precise biochemical mechanism of action can be ascertained, to determine the components of the DNA target that are essential for binding activity, and to identify other genes that are involved in the regulation of both the toxin genes and other genes that may be implicated in the disease process. These studies will be facilitated by the availability of the complete genome sequence of this pathogenic bacterium. The project will make a major contribution to our knowledge of how bacteria that cause disease are able to control the production of the toxins that are critical to the disease process. If we are to learn how to more effectively control and treat bacterial infections then it is very important that we understand the complex regulatory networks that tell bacteria when to produce its disease-causing products.Read moreRead less
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.