Some of the world's most important diseases, including important diseases of indigenous chilren and the hospitalised elderly are caused by bacteria that carry a surface coating called a capsule. It is not clear how this capsule is retained by bacteria. Resolution of this question could lead to the development of new disinfectants that will stop hospital-acquired infections, to new reagents that can be incoporated into medical devices where bacteria frequently grow, and new antibiotics.
Molecular Basis Of O-antigen Modification And Genomics Of Serotype-converting Bacteriophages Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection a ....There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection and subsequent incorporation of the virus into the genetic material of the bacterial cell result in modification of the bacterial O-antigen. This phage-mediated O-antigen modification gives rise to different serotypes. The project will address fundamental processes related to the O-antigen modification. This will be achieved by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster. We have isolated several serotype-converting bacteriophages from S. flexneri and we plan to compare and characterise their genomic information to increase understanding of their origin and relationship with the bacterial host.Read moreRead less
Identifying The Physiological Conditions That Promote Lateral Gene Transfer And Evolution Of New Streptococcal Pathovars
Funder
National Health and Medical Research Council
Funding Amount
$415,907.00
Summary
In the last few decades, the diseases caused by the three human pathogens, groups A, B and G streptococcus have undergone a transformation. The exchange of DNA between these species is speculated to play a role in this changing disease association. In this proposal we will identify the specific physiological and growth conditions that promote DNA transfer. Such information may help in our understanding of how new pathogenic strains of streptococci arise.
Polymicrobial Interactions In Chronic Periodontitis
Funder
National Health and Medical Research Council
Funding Amount
$413,133.00
Summary
In this study we will determine how three pathogenic species of bacteria interact. Together these species are associated with periodontitis and they produce toxic compounds that may cause tissue damage. Using the newly emerging technologies of metabolomics and transcriptomics we will characterise these interactions. This will identify potential diagnostic biomarkers of disease and therapeutic targets.
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
Characterising The Role Of Streptokinase Polymorphism In Invasive Pathogenesis Of Streptococcus Pyogenes.
Funder
National Health and Medical Research Council
Funding Amount
$480,535.00
Summary
Invasive bacterial pathogens such as Streptococcus pyogenes, can hijack host proteins and use them to facilitate the disease process. S. pyogenes secrete streptokinase to activate a host protease (plasminogen) which is used by the bacterium to invade through host tissue. This project will characterise the molecular mechanisms involved in streptokinase mediated activation of plasminogen which will assist the generation of novel therapeutics to treat invasive diseases.
Pathogenomics: New Ways To Exploit Genome Sequence Data From Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$547,372.00
Summary
Bacterial pathogens are locked in an evolutionary battle of survival with their eukaryote hosts. The rapidly evolving genes of medically-important pathogens are generally those required for adaptation to the human host. This project aims to exploit the abundance of available bacterial genome sequences to predict rapid evolution in bacterial pathogens using computational methods. The protein products of such genes offer novel targets for therapeutic intervention.
Protease-activated Receptor-1 (PAR-1) And Regulation Of Helicobacter Pylori Induced Mucosal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$478,090.00
Summary
Helicobacter pylori infections cause chronic gastritis which in some people results in stomach cancer or ulcers. We have identified a novel host factor, PAR-1, important for preventing this inflammation. We will use mice to identify how this molecule protects against gastritis and samples from patients to examine its importance in human disease. This will help explain why these diseases develop in some people but not others and perhaps allow identification of those at risk of developing disease.
Urinary Tract E. Coli: The Good Guys Versus The Bad Guys
Funder
National Health and Medical Research Council
Funding Amount
$296,150.00
Summary
Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that ....Escherichia coli is the primary cause of urinary tract infection (UTI) in the developed world. In Australia alone, E. coli affects more than 250,000 yearly to the extent where they require medical intervention. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime and in the USA UTIs result in $1.6 billion in medical expenses each year. Uropathogenic E. coli (UPEC) strains readily form biofilms on indwelling catheters and recent evidence suggests that they also form biofilm-like aggregates in the bladder. No treatment other than antibiotics (often inefficient due to resistance) is currently available. E. coli is also the most frequent cause of asymptomatic bacteriuria (ABU). ABU occurs in up to 6% of healthy individuals and affects high risk groups such as the elderly and diabetics. In general, most patients with ABU do not need treatment and in many cases the colonizing organism actually helps to prevent infection by other more virulent bacteria. The aim of this project is to compare UPEC and ABU E. coli for differences associated with virulence and biofilm growth. The project will generate a comprehensive and defined strain bank relative to E. coli that cause UTI. Understanding biofilm growth by this organism may lead to the development of improved and-or novel treatments. Furthermore, increased knowledge of ABU E. coli is essential if we are to fully explore the possibility of employing these organisms as probiotic agents to prevent infection by other pathogens in specific high risk patient groups.Read moreRead less