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.
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.
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
Role Of Regulatory Genes In The Gastrointestinal Pathogen, Clostridium Difficile
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
When patients are treated in hospital with antibiotics they sometimes develop chronic diarrhoea or colitis syndromes that are very difficult and expensive to treat. This project involves the analysis of the bacterium that generally causes these gastrointestinal diseases. We know that this microorganism is present in the hospital environment and that it produces potent protein toxins that are responsible for these diseases but we know little about the actual disease process. In most bacteria that ....When patients are treated in hospital with antibiotics they sometimes develop chronic diarrhoea or colitis syndromes that are very difficult and expensive to treat. This project involves the analysis of the bacterium that generally causes these gastrointestinal diseases. We know that this microorganism is present in the hospital environment and that it produces potent protein toxins that are responsible for these diseases but we know little about the actual disease process. In most bacteria that cause disease there are regulatory networks that control the expression of the genes responsible for the disease process. In this project, we aim to develop an understanding of how these regulatory networks operate in this particular bacterium. The latest techniques of molecular biology will be used to investigate several specific regulatory genes at the functional level. Since the entire DNA sequence of this bacterium is now known we will also use a broader research approach that makes use of this knowledge to examine all of potential regulatory networks that exist in this bacterium. Finally, we will develop new methods for the genetic analysis of the causative bacterium so that we will be better able to elucidate the role of specific genes in the disease process. By understanding how this bacterium controls the production of the proteins that interact with human intestinal cells to cause disease we hope to be able to prevent such diseases from occurring. The successful completion of the project therefore will make a major contribution to the development of improved methods for the control and treatment of these chromic diarrhoea and colitis syndromes.Read moreRead less
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
Inhibition Of Histidine Kinase Signal Sensing: A Novel Paradigm For Antimicrobial Development
Funder
National Health and Medical Research Council
Funding Amount
$464,144.00
Summary
Staphylococcus aureus (Golden staph) has been termed a superbug because of its remarkable ability to acquire resistance to virtually all antibiotics. Until recently, Golden Staph infections were almost always acquired in hospitals, but the increasing incidence of community-acquired S. aureus infections has rendered it a major public health threat in Australia. The aim of this research is to develop antimicrobial agents to combat antibiotic-resistant strains of Staphylococcus aureus.