Role Of Macrophages In Uropathogenic E. Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Urinary tract infections (UTI) are one of the most common types of infections in humans. They are also a major cause of septic shock, a condition with high fatality rates. Uropathogenic Escherichia coli (UPEC) are the major microbes causing UTI in humans. This project addresses the role of an immune cell type, the macrophage, in UPEC-mediated disease. The outcomes of this project will be a better understanding of how UPEC causes disease, and potentially new treatment regimes for UTI.
Halting The Spread Multidrug Resistant Uropathogenic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infection (UTI) and increasingly associated with resistance to multiple antibiotics. This project will study the virulence of multidrug resistant UPEC and use this knowledge to develop new approaches to treat and prevent UTI. The outcomes will be applicable to one of the most common infectious diseases of humans and have broad-reaching impact on our understanding of other infections caused by Gram-negative pathogens.
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.
A Matter Of Life And Death: Defining Novel Interactions Between Uropathogenic E. Coli And Macrophages That Influence UTI Pathology
Funder
National Health and Medical Research Council
Funding Amount
$643,060.00
Summary
Urinary tract infections (UTI) are one of the most common types of infections in humans. Uropathogenic Escherichia coli (UPEC) are the major microbes causing UTI in humans. This project will define novel interactions between UPEC and macrophages, an important immune cell involved in the control of UTI. The outcomes of this project will be a better understanding of how UPEC causes disease, and potentially new treatment regimes for UTI.
Understanding Uropathogenic E. Coli-mediated Subversion Of Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$932,536.00
Summary
Urinary Tract Infections (UTI) are one of the most common bacterial infections. Uropathogenic E. coli (UPEC) are the primary cause of UTI and increasingly associated with antibiotic resistance. UPEC use an array of strategies to overcome the innate immune system, which provides the first line of defence against infectious diseases. This project aims to understand how UPEC overcomes innate immunity, with the ultimate goal of devising new approaches for the treatment and prevention of UTI.
The Current Multidrug Resistant Escherichia Coli Pandemic: Exploring Novel Therapies Against The Predominant Culprit E. Coli ST131.
Funder
National Health and Medical Research Council
Funding Amount
$512,223.00
Summary
Escherichia coli ST131 is a pandemic superbug. Like MRSA, E. coli ST131 infections are resistant to multiple antibiotics and can become life threatening. This study will show how adhesion can be the 'Achilles' heel' of this global pathogen and how blocking E. coli ST131 adhesion offers an alternative therapy for multidrug resistant human infections. As we are left with no effective antimicrobials to treat E. coli ST131 infections, this work will provide novel outcomes that are sorely needed.
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.
Functional And Genomic Analysis Of The Globally Disseminated Multidrug Resistant Escherichia Coli ST131 Clone
Funder
National Health and Medical Research Council
Funding Amount
$825,537.00
Summary
Uropathogenic Escherichia coli (UPEC) is 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 and spread worldwide. This project uses genomic and high-throughput functional analysis methods to understand E. coli ST131 virulence and resistance. The outcomes of the work will be a better understanding of how E. coli ST131 causes disease, and potentially new treatment regim ....Uropathogenic Escherichia coli (UPEC) is 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 and spread worldwide. This project uses genomic and high-throughput functional analysis methods to understand E. coli ST131 virulence and resistance. The outcomes of the work will be a better understanding of how E. coli ST131 causes disease, and potentially new treatment regimes for UTI.Read moreRead less
Bacteriology Of Bronchiectasis In Australian Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$91,209.00
Summary
Many Indigenous children in the Northern Territory suffer from a chronic lung condition called bronchiectasis. This disease causes a lot of illness and can lead to early death in adulthood. Little is known about how the disease starts and how it can be prevented, but many children are being treated with the antibiotic azithromycin. My project aims to find out which bacteria are associated with bronchiectasis, how azithromycin affects the bacteria, and whether it leads to antibiotic resistance.