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
Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
Genes Of Mycobacterium Tuberculosis Essential For Latent Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
One third of the worlds population is latently infected with M. tuberculosis, the bacteria which causes TB. We have identified key genes in M. tuberculosis that enable the bacterium to shut-down and become latent. This project will investigate these genes, identify their role and yield vital information for a new paradigm of drug and vaccine development. Improved vaccines and drugs which can target and inhibit latency would be of enormous benefit to the global community.
Understanding The Role Of O-linked Glycosylation In Burkholderia Cenocepica For Host Survival Using Proteomic Approaches
Funder
National Health and Medical Research Council
Funding Amount
$222,004.00
Summary
The bacteria Burkholderia cenocepecia (Bc) is a common infection of Cystic Fibrosis suffers in Australia. ~20% CF patients infected with Bc will die due to lung failure. Due to this high death rate there is an urgent need to understand how Bc survives and causes disease in the host. This grant aims to understand how the attachment of sugars, a process known as glycosylation, affects the ability of Bc to survive in mammalian cells.
Host-pathogen Interactions In Clostridial Myonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$897,617.00
Summary
This project will show how the bacteria that cause gas gangrene interact with host cells in an infection. We will examine the expression of genes from both the host and the pathogen in a mouse disease model. The aims are to determine the impact of bacterial genes that are differentially regulated in an infected lesion, how gene expression of both the host and pathogen is modulated throughout the course of an infection and the role of host pathways in controlling the infection process.
The Glyco-interactome Of Pathogenic Neisseria: Understanding Disease And Defining Vaccine Targets
Funder
National Health and Medical Research Council
Funding Amount
$431,012.00
Summary
In order to infect humans and cause disease, many bacteria rely on interactions with carbohydrate (sugar) structures on human cells. This project aims to characterise the sugar interactions that enable Neisseria meningitidis (causes meningitis, sepsis) and Neisseria gonorrhoeae (causes gonorrhoea, associated with infertility and increased transmission of HIV) to cause disease. This will increase our understanding of host-pathogen interactions and aid development of new vaccines and therapeutics.
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
Using Genetic Tools To Study Helicobacter Pylori Pathogenesis And Persistence
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
H. pylori infection is the leading cause of gastric ulcer disease and stomach cancer. In light of emerging antibiotic resistance and failed vaccine trials, alternative therapies are needed to treat this lifelong infection. This project aims to develop tools to identify and characterize genes required by H. pylori for infection which will serve as new drug targets. This new knowledge will also contribute to a better understanding of the persistence of this and other bacteria.
Understanding Virulence In Staphylococcus Aureus And Impacts On Host Response
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Golden Staph remains an important cause of serious infections in Australian patients. New strategies to combat this disease require a better understanding of how Golden Staph causes disease and escapes the natural human response to infection. This study will provide new insights into how Golden Staph causes disease, and provide a platform for developing new strategies to prevent and treat Golden Staph infections.