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.
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
Multi-Targeted Inhibition Of An Essential Tetrameric Enzyme From Drug -Resistant Streptococcus Pneumonie.
Funder
National Health and Medical Research Council
Funding Amount
$534,313.00
Summary
Streptococcus pneumoniae is an significant human pathogen which causes several diseases including pneumonia and meningitis. Treatment of infection involves the use of antibiotics such as penecillin, however, resistant strains are now emerging. This project will address the real need to develop new antibiotics targeting this organism. This is essentially a drug discovery project which exploits a novel means to target Streptococcus pneumoniae.
The Pathogenesis Of Melioidosis: The Interaction Of Burkholderia Pseudomallei With Host Cells.
Funder
National Health and Medical Research Council
Funding Amount
$344,375.00
Summary
Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen a ....Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen and liver, acute localised suppurative infection and pneumonia. Melioidosis may also become latent, and later develop into an acute and fatal infection. It is important to understand, at the molecular level, how and why the causative bacterium is able to cause disease. Only with such an understanding can measures be undertaken to prevent the disease, or novel methods developed to control the disease. Colonisation of a host is a first step in the disease process for all bacteria which cause disease. Large protein molecules located on the surface of disease-causing bacteria are usually neccessary for colonisation of the host since they allow adherence to the surface of host cells. We have previously undertaken a basic study of adherence. This study will build on this research with the aim of identifying molecules which mediate adherence to host cells, using in vivo and in vitro methods, including the techniques of molecular biology. This study will inevitably lead to the development of vaccine candidates which is important to the management of melioidosis, particularly in high risk groups. It may also allow the development of novel antimicrobial compounds.Read moreRead less
Investigation Of The Effects Of Polymicrobial Infection On The Induction Of Otitis Media
Funder
National Health and Medical Research Council
Funding Amount
$235,511.00
Summary
Middle ear infection is a highly prevalent paediatric disease characterised by an inflammation of the middle ear and is the most prevalent illness of childhood. It is reported that greater than 80% of children have had at least one episode of acute otitis media by 3 years of age and almost 40% of children have more than 6 episodes by age 7 years. The cause and pathogenesis of middle ear infection are multifactorial and influence of prevalence and chonicity of the infections. Prevention of bacter ....Middle ear infection is a highly prevalent paediatric disease characterised by an inflammation of the middle ear and is the most prevalent illness of childhood. It is reported that greater than 80% of children have had at least one episode of acute otitis media by 3 years of age and almost 40% of children have more than 6 episodes by age 7 years. The cause and pathogenesis of middle ear infection are multifactorial and influence of prevalence and chonicity of the infections. Prevention of bacterial middle ear infection caused by Streptococcus pneumoniae, nontypeable Haemophilus influenzae and Moraxella catarrhalis requires a much better knowledge of how these bacteria interact with each other and with the host. The poor efficacy of the current pneumococcal paediatric vaccine for preventing middle ear infections highlights this deficiency in our knowledge and will impede the development of a suitable multvalent vaccine to prevent infection by the 3 major bacterial pathogens. This study will investigate how the bacteria colonising the respiratory tract interact during infection and how they affect the host.Read moreRead less
Role Of The Host Fibrinolytic System In Invasive Group A Streptococcal Disease
Funder
National Health and Medical Research Council
Funding Amount
$531,444.00
Summary
The flesh-eating bacterium group A streptococcus (GAS) is estimated to cause 700 million cases of self-limiting disease, and 600,000 cases of serious invasive disease each year. Approximately 25% of invasive infections are fatal. We have shown that GAS are able to hijack the host fibrinolytoc system to cause severe invasive infections. We plan to further examine the details of how this contributes to GAS disease. This research may contribute to the future devlopment of new therapeutics.
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.
Functional Biology Of Large Serine Recombinases From Mobile Antibiotic Resistance Elements
Funder
National Health and Medical Research Council
Funding Amount
$436,328.00
Summary
In recent years there has been increasing concern about the emergence of multiply antibiotic resistant strains of many common bacterial pathogens. The development of multiple resistance phenotypes has already led to compromises in the ability to successfully treat infected patients and to increased treatment costs. The emergence of these resistant bacteria is the result of excessive or inappropriate use of antibiotics and the ability of antibiotic resistance genes to be transferred from resistan ....In recent years there has been increasing concern about the emergence of multiply antibiotic resistant strains of many common bacterial pathogens. The development of multiple resistance phenotypes has already led to compromises in the ability to successfully treat infected patients and to increased treatment costs. The emergence of these resistant bacteria is the result of excessive or inappropriate use of antibiotics and the ability of antibiotic resistance genes to be transferred from resistant to susceptible bacteria, either within or between bacterial species. The movement of resistance elements that are integrated into the bacterial genome often involves their excision from their existing site and their subsequent integration into another site in the same or a different genome. This project centres on the analysis of this process in resistant bacteria that cause major disease problems in our hospitals. The research project will focus on MRSA (Multiply Resistant Staphylococcus aureus) which has been a serious problem in our hospitals for many years, and Clostridium difficile, an emerging pathogen of increasing importance and which causes a very serious and chronic form of colitis in hospital patients. By studying the biochemical processes by which enzymes called recombinases excise and subsequently integrate antibiotic resistance elements from these bacteria and by determining the three dimensional structure of such enzymes we aim to determine the mechanism of action of members of this important enzyme family. The major outcomes of the project will be an increased understanding of one of the major processes by which antibiotic resistance determinants can spread both within and between bacterial pathogens of importance in the hospital environment. These studies will contribute towards the development of improved methods for controlling the spread of resistant pathogens and resistance genes in the hospital environment, with concomitant benefits to human health.Read moreRead less