Functional Biology Of Large Serine Recombinases From Mobile Antibiotic Resistance Elements
Funder
National Health and Medical Research Council
Funding Amount
$436,328.00
Summary
In recent years there has been increasing concern about the emergence of multiply antibiotic resistant strains of many common bacterial pathogens. The development of multiple resistance phenotypes has already led to compromises in the ability to successfully treat infected patients and to increased treatment costs. The emergence of these resistant bacteria is the result of excessive or inappropriate use of antibiotics and the ability of antibiotic resistance genes to be transferred from resistan ....In recent years there has been increasing concern about the emergence of multiply antibiotic resistant strains of many common bacterial pathogens. The development of multiple resistance phenotypes has already led to compromises in the ability to successfully treat infected patients and to increased treatment costs. The emergence of these resistant bacteria is the result of excessive or inappropriate use of antibiotics and the ability of antibiotic resistance genes to be transferred from resistant to susceptible bacteria, either within or between bacterial species. The movement of resistance elements that are integrated into the bacterial genome often involves their excision from their existing site and their subsequent integration into another site in the same or a different genome. This project centres on the analysis of this process in resistant bacteria that cause major disease problems in our hospitals. The research project will focus on MRSA (Multiply Resistant Staphylococcus aureus) which has been a serious problem in our hospitals for many years, and Clostridium difficile, an emerging pathogen of increasing importance and which causes a very serious and chronic form of colitis in hospital patients. By studying the biochemical processes by which enzymes called recombinases excise and subsequently integrate antibiotic resistance elements from these bacteria and by determining the three dimensional structure of such enzymes we aim to determine the mechanism of action of members of this important enzyme family. The major outcomes of the project will be an increased understanding of one of the major processes by which antibiotic resistance determinants can spread both within and between bacterial pathogens of importance in the hospital environment. These studies will contribute towards the development of improved methods for controlling the spread of resistant pathogens and resistance genes in the hospital environment, with concomitant benefits to human health.Read moreRead less
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
Worldwide Molecular Analysis Of Streptococcus Pyogenes Scarlet Fever Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$544,041.00
Summary
The microorganism group A Streptococcus (also called GAS or Streptococcus pyogenes) ranks among the top 10 infectious disease killers of humans. Recently, outbreaks of scarlet fever have occurred in both Asia and the United Kingdom, placing a serious strain on health systems. The reasons underlying these outbreaks remain unknown. Our team will lead the global effort to characterise this rise in scarlet fever, and provide recommendations and solutions to health professionals.
Protein Glycan Interactions In Infectious Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$9,182,220.00
Summary
Infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing microbes and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat infectious diseases in the 21st centu ....Infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing microbes and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat infectious diseases in the 21st century.Read moreRead less
Comparative And Functional Genomics Of Human Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$601,484.00
Summary
Bacteria have evolved different ways of causing disease in humans. Some bacteria produce toxins that attack the host or they have developed ways to persist in the host by evading immune responses and resisting antibiotics. This project is concerned with understanding how these processes occur and developing preventative strategies for two important groups of bacteria that cause disease in humans, including the bacteria that cause TB and the devastating skin disease Buruli ulcer, and the hospital ....Bacteria have evolved different ways of causing disease in humans. Some bacteria produce toxins that attack the host or they have developed ways to persist in the host by evading immune responses and resisting antibiotics. This project is concerned with understanding how these processes occur and developing preventative strategies for two important groups of bacteria that cause disease in humans, including the bacteria that cause TB and the devastating skin disease Buruli ulcer, and the hospital superbug "Golden Staph".Read moreRead less
Pathogenesis, Treatment And Prevention Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$852,458.00
Summary
Bacterial infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. My research program aims to better understand the dynamic interactions between major disease-causing bacteria and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat bacterial infectious diseases in the 21st century.
Preclinical Studies Of Group A Streptococcal Vaccine Candidates
Funder
National Health and Medical Research Council
Funding Amount
$532,492.00
Summary
Group A streptococcus causes 520,000 deaths each year. A safe and effective vaccine is not commercially available. We have identified 2 new protective candidate antigens, and we seek to undertake critical preclinical studies to provide further proof-of-concept data. This work will underpin commercial decisions by our industry partner (Wyeth) leading to human trials and the development of a safe group A streptococcal vaccine for human use.
Crohn’s disease (CD), an inflammatory disorder of the gut, is thought to result from an inappropriate response to an environmental trigger, likely gut bacteria. This project will assess differences in microbial communities and host gene expression of early- and late-stage CD tissues. A greater understanding of the differences in mucosal gene expression induced by specific bacteria may provide insights into the pathophysiology of CD, and could conceivably guide therapeutic choices in the future.