MOLECULAR ANALYSIS OF VIRULENCE FACTORS OF GROUP B STREPTOCOCCI
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Streptococcus agalactiae, more commonly referred to as group B streptococcus (GBS), is the commonest cause of life-threatening infection (specifically bacteraemia, pneumonia and meningitis) in neonates. Mortality is high even in developed countries where antimicrobial therapy is readily available. In spite of the importance of GBS disease, the precise molecular mechanisms whereby the organism colonizes, invades and damages host tissues are poorly understood. The long term goal of this project is ....Streptococcus agalactiae, more commonly referred to as group B streptococcus (GBS), is the commonest cause of life-threatening infection (specifically bacteraemia, pneumonia and meningitis) in neonates. Mortality is high even in developed countries where antimicrobial therapy is readily available. In spite of the importance of GBS disease, the precise molecular mechanisms whereby the organism colonizes, invades and damages host tissues are poorly understood. The long term goal of this project is to gain a complete understanding of the pathogenesis of GBS disease and to apply this to development of improved preventative strategies. We propose to carry out a comprehensive molecular characterization of genes encoding putative GBS virulence determinants, with particular reference to those which encode the capacity to adhere to and invade host cells. GBS carrying defined mutations in these genes will be constructed and their virulence will be compared with that of the otherwise isogenic parental GBS. This will enable us to determine the precise contribution of each putative virulence factor to the pathogenesis of disease. Moreover, proteins shown to be important in this process will be tested for vaccine potential.Read moreRead less
Translating Bacterial Molecular Epidemiology Into Information To Improve Infectious Disease Risk Assessment And Control
Funder
National Health and Medical Research Council
Funding Amount
$494,500.00
Summary
Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which shou ....Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which should be partly off-set by immunisation. Giving antibiotics during labour, to women colonised with GBS, can reduce infection rates in newborns, but there are many disadvantages of this approach, including the risk of increased antibiotic resistance. Vaccines against GBS are mpt yet available. We have developed methods to identify detailed fingerprints of these bacteria which allow us to identify types, antibiotic resistance and, for GBS, other characteristics which can distinguish highly pathogenic strains from the majority that are carried harmlessly and unlikely to cause disease. The methods are still quite slow and expensive and produce complex patterns,which are difficult to interpret rapidly. We plan to develop a new, rapid and relatively inexpensive, fingerprinting system for these bacteria and computer programs to analyse and interpret the results. They will allow us to check the strains of pneumococci that cause disease to make sure that new ones, not covered by the vaccine, do not become more common and reduce the effectiveness of vaccine and that antibiotic resistance does not increase further. The methods will also allow us to study differences between the small proportion of GBS strains that cause neonatal infection and the majority that are carried harmlessly by pregnant women and are of little risk to their babies. Eventually this should allow doctors to identify women whose babies are most at risk, reduce unnecessary antibiotic use.Read moreRead less
Urinary tract infections are among the most common infectious diseases in humans, with approximately 40% of adult women having experienced at least one. I aim to characterise and compare the dynamics of the innate immune response in the urinary tract, in response to uropathogens and characterise bacterial factors affecting such responses. Understanding immune function provides important new understanding into these disease processes that may result in the development of new treatment approaches.
Worldwide Molecular Analysis Of Streptococcus Pyogenes Scarlet Fever Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$544,041.00
Summary
The microorganism group A Streptococcus (also called GAS or Streptococcus pyogenes) ranks among the top 10 infectious disease killers of humans. Recently, outbreaks of scarlet fever have occurred in both Asia and the United Kingdom, placing a serious strain on health systems. The reasons underlying these outbreaks remain unknown. Our team will lead the global effort to characterise this rise in scarlet fever, and provide recommendations and solutions to health professionals.
Construction And Immunogenic Evaluation Of Hepatitis B Virus Like Particles Expressing T And B Cell Epitopes Of Streptococcus Pneumoniae For The Prevention Of Hepatitis B And Pneumococcal Mediated Otitis Media In Australian Indigenous Children.
Funder
National Health and Medical Research Council
Funding Amount
$500,637.00
Summary
Australian Indigenous children suffer abormally high levels of middle ear infections (term otitis media). In many cases the infections become chronic and have a severe dischage. We propose to make a novel vaccine that will protect these children against a major bacterial cause of the ear infection as well as against hepatitis B virus infection as well.
Characterisation Of Immune Responses To Sarcoptes Scabiei Cysteine Proteases, Group 1 Allergen Homologues, In Scabies
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly ....Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly dreadful form of scabies, known as crusted scabies, can develop in a minority of people, in which mites multiply in their millions and the affected person develops severe crusting of the skin. This has resulted in death within 5 years for up to 50% of people with this form of scabies. Scabies mites are scientifically very similar to house dust mites, and they produce cross reactive proteins. Molecular studies in our laboratory have enabled the identification and cloning of a number of scabies molecules with considerable similarity to known house dust mite proteins that cause allergic disease. In this study we propose to focus on a group of scabies proteins with significant identity to the extensively studied Group 1 house dust mite allergens, reported to cause an immune response in 90% of mite allergic people. We propose to use these scabies mite molecules to characterise the immune response in ordinary scabies and compare it to the more severe and debilitating crusted form of the disease. Characterisation of the immune response in scabies will ultimately aid in the development of new treatment for crusted scabies based on immunotherapy. Studies will also investigate for any cross reactivity with the house dust mite group 1 molecules and enable the design of specific immunodiagnositics to distinguish house dust mite allergy from scabies infestation and thus facilitate early diagnosis of scabies carriers and better control of the infestation in endemic communities.Read moreRead less