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
The Role Of N-linked Protein Glycosylation In Campylobacter Jejuni Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$757,600.00
Summary
Protein glycosylation is crucial in enabling C. jejuni to colonize poultry, which is the most common route to human infection. The roles played by this modification remain almost completely unknown yet are likely to be multi-factorial. This project will determine the function of glycosylation and thus lead to eventual interventions aimed at reducing the organism in poultry for human consumption.
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.
Uncovering Novel Roles Of Escherichia Coli Flagella And LPS In Uropathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$404,677.00
Summary
Urinary tract infections (UTI) are common infectious diseases in humans. Uropathogenic Escherichia coli (UPEC) cause most UTI. UPEC produce factors that promote their survival and influence disease such as flagella. We have identified anti-inflammatory responses as a key element of UTI and have shown that these responses contribute to control of UTI. In this project, we will investigate how the UPEC flagella component, FliC, contributes to anti-inflammatory responses and what this means for UTI.
Understanding The Impact Of Epigenetic Gene Regulation On Helicobacter Pylori Persistence And Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$757,896.00
Summary
Helicobacter pylori is a highly persistent pathogen and remains a significant problem worldwide, causing gastritis, peptic ulcer disease and gastric cancer. This project will increase our understanding of how H. pylori infection persists for the life of its human host and will provide knowledge that is critical in developing new strategies for preventing these infections.
Mechanisms Of Disease Caused By Hospital-acquired Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$465,218.00
Summary
We are currently experiencing unprecedented levels of antibiotic resistance in human pathogens. Unfortunately, the drug development pipeline is drying up, with almost no novel therapeutic options expected in the near future. This proposal aims to identify the mechanisms by which the most important antibiotic-resistant human pathogens make us sick. The expected outcomes are the identification of new targets that may be amenable to future drug development. These targets are aimed at making the org ....We are currently experiencing unprecedented levels of antibiotic resistance in human pathogens. Unfortunately, the drug development pipeline is drying up, with almost no novel therapeutic options expected in the near future. This proposal aims to identify the mechanisms by which the most important antibiotic-resistant human pathogens make us sick. The expected outcomes are the identification of new targets that may be amenable to future drug development. These targets are aimed at making the organisms less capable of causing disease in humans.Read moreRead less
Death Receptor Signaling During E. Coli And Salmonella Infection
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Upon encountering invading microorganisms, the body’s immune system usually initiates an inflammatory response to recruit populations of immune cells to the site of infection. To counter this attack, many bacterial pathogens have evolved distinct ways of disarming the inflammatory response. We are investigating the discovery that gastrointestinal bacteria such as Salmonella and pathogenic E. coli specifically interfere with the messages sent by the body’s innate sensors to recruit killer immune ....Upon encountering invading microorganisms, the body’s immune system usually initiates an inflammatory response to recruit populations of immune cells to the site of infection. To counter this attack, many bacterial pathogens have evolved distinct ways of disarming the inflammatory response. We are investigating the discovery that gastrointestinal bacteria such as Salmonella and pathogenic E. coli specifically interfere with the messages sent by the body’s innate sensors to recruit killer immune cells.Read moreRead less
Targeting Glycointeractions To Generate New Opportunities To Treat And Prevent Bacterial Infections.
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Bacteria and bacterial toxins can interact with complex sugar structures on human cells called glycans. My research team has identified new and important glycan interactions used by bacteria that cause diseases ranging from pneumonia, meningitis and food borne infections to urinary tract and sexually transmitted diseases. Now that these interactions have been discovered, they can be exploited to create drugs and vaccines that may treat and prevent disease by blocking the glycan interactions.