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NOVEL SOLUTIONS FOR ANTIMICROBIAL RESISTANT PATHOGENS
Funder
National Health and Medical Research Council
Funding Amount
$474,513.00
Summary
Antibiotic resistance and infections caused by superbugs are major public health concerns. My fellowship aims to develop new strategies to prevent and treat infections caused by resistant superbugs. I will use innovative approaches both in the laboratory and in the hospital setting, and foster research across multiple groups, to solve “real-life” clinical problems. The proposed work will improve the outcomes for the most vulnerable hospitalised patients.
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
Metabolism-driven Interactions Of Non-typeable Haemophilus Influenzae And Its Host: A Critical Factor In Infection?
Funder
National Health and Medical Research Council
Funding Amount
$474,932.00
Summary
Non-typeable Haemophilus influenzae (NTHi) is the underlying cause of many severe acute and chronic respiratory infections, which represent a significant burden to the healthcare system. As NTHi is unable to survive outside the human host, it is is highly adapted to survival in the body niches it colonizes. We are investigating how NTHI is able to survive in the presence of tissue inflammation, and whether it contributes to the inflammatory process through some of its metabolic products.
The Impact Of Pseudomonas Aeruginosa Biofilm On Eye Infection And The Development Of Antimicrobial Contact Lenses
Funder
National Health and Medical Research Council
Funding Amount
$328,932.00
Summary
Worldwide, 125 million people correct their vision through the use of contact lenses. Contact lens use predisposes the wearer to sight threatening eye infections. Despite advanced material technology and improved hygiene regimens, the rate of contact lens-related infectious disease has remained constant. This research aims to elucidate how bacteria compromise the ocular immune system in order to develop preventative/therapeutic strategies to combat ocular infections.
Molecular Analysis Of Endocarditis Causing Strains Of Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$110,960.00
Summary
"Staphylococcus aureus" or "Golden Staph” is one of the principal causes of infective endocarditis, the infection of the endocardial surfaces of the heart and heart valves that may result in valvular insufficiency and eventual heart failure. This work will define the molecular mechanisms that allow S. aureus to survive and persist on endocardial surfaces. Such insight may lead to new future treatment regimes for infective endocarditis.
Infectious diseases plague mankind; with infections responsible for approximately 20% of all deaths worldwide. New strategies are urgently needed and we have positioned our research to address questions around how to forestall bacterial pathogens in the initial phases of invasion of human tissues and provide full understanding of the key molecules on the surfaces of bacterial cells. This fundamental knowledge is crucial to new drugs, vaccines and infection-resistant medical devices.
Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infections (UTI) and sepsis. Recently, a highly virulent clone of UPEC (E. coli ST131) that is resistant to multiple types of antibiotics has emerged worldwide. This project addresses the mechanisms by which E. coli ST131 can colonise the urinary tract and cause disease. The outcomes of this project will be a better understanding of how E. coli ST131 causes disease, and potentially new treatment regimes for UTI.
Molecular Characterization Of E. Coli That Cause Urinary Tract Infection
Funder
National Health and Medical Research Council
Funding Amount
$387,114.00
Summary
The long term goals of the proposed research are to understand the processes by which uropathogenic Escherichia coli (UPEC) cause acute, recurrent and chronic infections and to identify new UPEC targets for therapeutic intervention. 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 more than 1 million hospitalizations and $1.6 billion in medical expenditures each year. It is estimated ....The long term goals of the proposed research are to understand the processes by which uropathogenic Escherichia coli (UPEC) cause acute, recurrent and chronic infections and to identify new UPEC targets for therapeutic intervention. 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 more than 1 million hospitalizations and $1.6 billion in medical expenditures each year. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime. The recurrence rate is high and no treatment other than antibiotics (often inefficient) is currently available. UPEC are the primary cause of UTI. In the last grant period, we focused on the molecular interplay that exists between different surface adhesins of UPEC. We succeeded in demonstrating functional interference between adhesins, motility organelles, aggregation factors and the capsule. We also discovered and partially characterized several novel UPEC adhesins that may play a role in pathogenesis. We established two novel technology sets: a mouse model of ascending UTI and the flow chamber biofilm model. In the next grant period, we will build on these concepts and experimental systems to gain a deeper understanding of the molecular mechanisms underlying UPEC virulence. We will characterize the role of several novel UPEC surface proteins in cell adhesin, aggregation, biofilm formation and colonization of the mouse urinary tract. We will employ an integrated approach that combines a powerful bacterial genetic system, a biofilm model, a mouse UTI model, microscopy and tissue culture systems to reveal the cellular, molecular, and structural basis for the pathogenesis of UTI. The work will facilitate the development of new vaccine approaches to prevent UTI, such as novel mechanisms for strain attenuation and vaccine design. The burden of UTI disease demands such research endeavours.Read moreRead less
Role Of Autotransporter Proteins In Uropathogenic E. Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$611,149.00
Summary
Urinary tract infections (UTI) are among the most common infectious diseases of humans. Uropathogenic E. coli (UPEC), the primary cause of UTI, utilize a range of adherence mechanisms to colonize the urinary tract. In this project we will characterise the function and mode of secretion for one important class of UPEC adherence factors – autotransporter proteins. This work may inform new approaches to prevent UTI, an urgent need given the rapid increase in resistance to antibiotics among UPEC.
The Effect Of Defective Iron Handling On Immune Function And Pseudomonas Aeruginosa Infection In The Cystic Fibrosis Lung
Funder
National Health and Medical Research Council
Funding Amount
$97,213.00
Summary
In this research higher degree I will study the effects of iron on airway sepsis in cystic fibrosis (CF), with a particular focus on the major pathogen Pseudomonas aeruginosa. Increased concentrations of iron have been described in the CF lung, and CF airway epithelial cells display abnormal iron handling which facilitates P. aeruginosa growth. I will explore imposed iron limitation combined with conventional antibiotics as a new therapeutic strategy for treatment of chronic airway infection.