Evolution And Function Of A Novel Lateral Flagellar Locus, Flag-2, In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$465,158.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified a novel genetic region that allows E. coli to survive and persist in the intestine. Similar genes are also present in closely related organisms. This project will help us to undestand how new diseases evolve and emerge and may lead to the development of new vaccines to protect against infant diarrhoea.
Contribution Of Nuclear Targeting Of The NleE-OspZ Family Of Proteins To Escherichia Coli And Shigella Virulence
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified new bacterial proteins that allow E. coli to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Shigella which causes dysentary. We will determine how these proteins act by finding the host cell proteins they bind.
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.
A Novel CD39-like Ecto-NTPDase Of Legionella Pneumophila
Funder
National Health and Medical Research Council
Funding Amount
$362,046.00
Summary
Legionnaire's disease is a serious cause of community acquired pneumonia. We are studying the way the Legionella bacteria persist in the environment and cause disease. We have found that Legionella produces a specific protein that mimics the action of a human protein. This proposal aims to work out how the bacteria use this protein to infect the human lung and escape killing by immune cells. The results from this study will help to determine if this protein may be used as a target for the develo ....Legionnaire's disease is a serious cause of community acquired pneumonia. We are studying the way the Legionella bacteria persist in the environment and cause disease. We have found that Legionella produces a specific protein that mimics the action of a human protein. This proposal aims to work out how the bacteria use this protein to infect the human lung and escape killing by immune cells. The results from this study will help to determine if this protein may be used as a target for the development of new anti-infective drugs.Read moreRead less
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.
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
Characterisation Of Enterohaemorrhagic Escherichia Coli Lacking Classical Virulence Markers
Funder
National Health and Medical Research Council
Funding Amount
$140,660.00
Summary
Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this ty ....Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this type of E.coli and usually acquire the infection by consuming contaminated food or water. This organism is currently a global food safety problem and the bacteria are especially prevalent in ground beef products and water or vegetables that have been contaminated with cattle faeces. In this study we aim to identify new bacterial genes and proteins that may be used to improve current means of detecting and diagnosing this kind of E.coli. A great deal is known about the way in which the classical strains of this virulent E .coli colonise the intestine however a small but significant group of these organisms do not carry known colonisation factors. We aim to identify bacterial proteins in these non-classical strains of E.coli which are needed for attachment of the bacteria to the host. Identifying how these bacteria interact with the host may help us to develop improved means of detecting and diagnosing this life-threatening infection.Read moreRead less
Identification Of Type III Effectors In Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Salmonella is a major cause of disease across the world. In order to cause disease, Salmonella injects certain molecules into our own human cells to reprogramme them to promote Salmonella infection. This work aims to identify a large proportion of those molecules injected by Salmonella. Once identified, a more complete understanding of exactly how Salmonella reprogrammes our cells will be possible, enabling new avenues for therapeutics.
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder. The work has implications for the development of new approaches to prevent and treat UTI.
Characterisation Of Extracellular DNases Of Pseudomonas Aeruginosa And Their Contribution To Disease
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
The bacterium Pseudomonas aeruginosa causes a number of serious diseases of humans particularly of immunocompromised patients. We have found that this bacterium secretes enzymes that have the ability to digest DNA. This proposal aims to work out how this bacterium uses these enzymes to infect human tissues and escape killing by immune cells. The results from this study will help to determine if these proteins may be used as targets for the development of new anti-infective drugs.