Characterization Of The Type IX Secretion System In Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$831,656.00
Summary
Periodontitis is associated with the keystone pathogen Porphyromonas gingivalis. We have identified a novel protein secretion machine comprised of at least 12 components in P. gingivalis which transports the bacterium's major virulence factors to the cell surface and attaches them to the outer membrane. We aim to determine the spatial arrangement and specific role of each of these 12 components and thereby provide targets for future treatments against this disease.
Role Of Hypoxia Inducible Factor In Innate Immune Function Against Gram-positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$241,352.00
Summary
Our society is currently facing the rise of drug-resistant pathogens ("superbugs") such as the potentially devastating methicillin-resistant Staphylococcus aureus, or _MRSA�. Recently, a molecule known as HIF has been shown to control the ability of our white blood cells to kill bacteria. This proposal aims to investigate the use of HIF boosting drugs to treat infections. These novel HIF agonists could be used alongside conventional antibiotics to improve infectious disease.
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.
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
Exploitation Of Bacterial Transcription Initiation As A Target For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Antibiotic resistant infections from 'superbugs' are a major health problem. We will exploit information we have gathered on the machinery that copies genetic information into a message to discover chemical compounds that can be used for the development of new antibiotics with a novel mechanism of action.
Impact Of Influenza A Infection On T Cell-mediated Immunity To Pulmonary Tuberculosis.
Funder
National Health and Medical Research Council
Funding Amount
$488,058.00
Summary
Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of B ....Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of BCG.Read moreRead less
Targeting Lagging Strand DNA Replication In Model And Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$590,426.00
Summary
An increasing concern is the growing number of hospital acquired infections that cannot be treated effectively with antibiotics because the bacteria that cause them are resistant to drug treatments. This project will develop our basic understanding of how DNA is copied in bacteria that are about to reproduce themselves, and we will use this knowledge to discover ways to stop them from copying their DNA, thus killing them. This will provide the foundation for development of new antibiotics.
Structural Studies Of Bacterial Pore-forming Protein Toxins
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
In this project the three-dimensional structures of proteins that form pores in membrane cell walls will be determined. These proteins are bacterial toxins and knowledge of their structure may prove useful in the design of new antibiotics. This project will focus on a class of toxins called the cholesterol-dependent cytolysins which are released by Gram positive bacteria such as Clostridia and Streptococcus and which cause a variety of nasty infectious diseases such as gas gangrene, pneumonia an ....In this project the three-dimensional structures of proteins that form pores in membrane cell walls will be determined. These proteins are bacterial toxins and knowledge of their structure may prove useful in the design of new antibiotics. This project will focus on a class of toxins called the cholesterol-dependent cytolysins which are released by Gram positive bacteria such as Clostridia and Streptococcus and which cause a variety of nasty infectious diseases such as gas gangrene, pneumonia and meningitis. The three-dimensional structures will be elucidated using X-ray crystallography. Protein crystallography is the study of three-dimensional shapes of proteins at near atomic resolution. In this method proteins are made to form crystals. X-ray beams are then shone on the crystals causing the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge of the structure of proteins is necessary for the complete understanding of their biological activity and is also very useful for the rational design of new drugs that may alter their activity.Read moreRead less
Understanding The Complex Relationship Between Host, Pathogen And Antibiotic Factors On Treatment Outcome In Serious Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$380,945.00
Summary
Millions of people still die every year from bacterial infections despite the availability of antibiotics. The same bacterial infection in one person can behave very differently in another person, so infections can range from trivial to life-threatening or fatal. Understanding the relationship between the patient, the infecting bacteria and the antibiotic treatment given will ultimately help to predict and improve outcomes for patients with serious bacterial infections.
The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Te ....The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Team has demonstrated that the Team is at the forefront of research in this area. The novel antibiotics work by preventing bacteria sticking to surfaces and by preventing the bacteria from releasing toxins. The studies will concentrate on those bacteria that produce infections in the lungs (acute pneumonia), eyes (corneal infection), ear (middle ear disease), and abscesses.Read moreRead less