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
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