Anti-sporulation Strategies For Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$651,559.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These strains have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains spread and will provide knowledge that is critical for developing improved strategies for preventing these infections.
A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a ....A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a population some cells will lack genes that others have. Some of these shared genes apart from antibiotic resistance can be a concern and include traits that make some bacteria pathogenic. Thus, two cells of the same species may have very different abilities to cause disease based on what additional genes they carry. Genomics is becoming one of the great scientific revolutions of the 21st century. Over 160 microbial genomes have been sequenced to date and from these studies we have also learned many important things including how some bacteria cause disease. Mobile DNA presents unique challenges to microbial genomics however since different individuals in a species can have many different genes. Thus genomics on even many individuals of a species may miss bacterial genes important to us. Here we will be applying genomics in a way that specifically targets those genes that are shared. This will have many benefits. We will be able to greatly increase our rate of discovery of medically important and other genes in way that is targeted. This approach will allow us to discover these shared genes in a way that is much more cost effective and faster than conventional whole cell genomics. It will also allow us to gain an understanding of how benign bacteria associated with humans may act as reservoirs for passing on harmful genes to bacteria that cause hospital infections.Read moreRead less
The development and evaluation of a new therapy for the prevention and treatment of bacterial infections in hospitals. The technology used in this project will enable products to be developed from the Australian dairy industry which may safely provide protection and treatment for diarrhoea acquired in hospitals for which there are few effective options. The product will be cost effective and can be used as a public health tool to control outbreaks in those most susceptible to severe disease.
Linking Genomics Of Burkholderia Pseudomallei To Melioidosis: Diversity Of Clinical Manifestations, Changing Epidemiology And Microevolution In Chronic Carriage.
Funder
National Health and Medical Research Council
Funding Amount
$602,769.00
Summary
The Darwin Prospective Melioidosis Study has documented 761 cases since 1989, with 102 fatalities. This study has led to improved therapy and public health initiatives. New technology to sequence whole bacterial genomes provides an opportunity to determine why urban melioidosis is increasing and to analyse this unique 22+ year set of bacteria and their linked patient data to find the important bacterial virulence factors, forming a foundation for future diagnostics, therapeutics, and vaccines.
Functional characterisation of poly-histidine triad proteins. This project aims to understand the role and function of a novel family of surface proteins produced by Streptococci. These so-called polyhistidine triad proteins are known to contribute to capacity to cause disease in animals and humans, but we need to know how they work, as they may be excellent targets for novel drugs or vaccines.
Novel perspectives on the function of AB5 toxin B subunits in pathogenic bacterial. AB5 toxins are produced by bacteria that cause important diseases in humans and livestock. This project tests the hypothesis that the components of the toxins responsible for binding to host cells and tissues also directly contribute to cellular damage, thereby providing a better understanding of how AB5 toxin-producing bacteria cause disease.
How bacteria cause disease in the urinary tract. This project will investigate the virulence properties of uropathogenic Escherichia coli, the major causative agent of urinary tract infections (UTI) in humans. The results will help to understand how these bacterial pathogens cause disease and will impact strategies aimed at the prevention and treatment of chronic and recurrent UTI.
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
A One Health Approach To Assessing The Threat Of Clostridium Difficile To Australia’s Biosecurity: A Genomic Investigation Of Human, Animal And Environmental Isolates
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Clostridium difficile is a bacterium that causes life-threatening diarrhoea in humans and animals and is a major public health issue in Australia. This project will study the genetic make-up of the bacterium and identify factors contributing to the emergence, evolution, and spread of C. difficile. This knowledge will be essential in guiding effective public health interventions and reducing deaths from C. difficile infection in humans and animals.
Defining The Role Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$870,925.00
Summary
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $1 billion annually. This proposal aims to define the role of the transition metal zinc in innate immune resistance to bacterial infection. This knowledge will reveal new targets for next generation antimicrobial therapeutics.