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.
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
Interrogation Of Streptococcal Genomic Epidemiology Within Disease Endemic Regions
Funder
National Health and Medical Research Council
Funding Amount
$325,896.00
Summary
Group A streptococcal (GAS) bacterial infections within the Indigenous populations of Northern Australia are amongst the highest in the world. This project uses comparative bacterial genomics to examine current and historical outbreaks of GAS disease in Northern Australia relative to globally sourced GAS. This will be used to examine the spread of disease causing GAS between remote communities as well as investigating genetic markers of disease and informing therapeutic interventions.
Role Of Streptococcus Agalactiae Glyceraldehyde 3-phosphate Dehydrogenase (GAPDH) In Infection And Potential As A Target To Control Colonization In The Female Genital Tract
Funder
National Health and Medical Research Council
Funding Amount
$677,177.00
Summary
Extracellular proteins produced by pathogenic bacteria can facilitate microbial colonization of the host by mediating binding to host cells and by modulating the immune system. These proteins exert their effects by subverting specific elements of the immune system and this can allow infection to worsen. This project will increase our understanding of how this bacterium chronically colonizes humans and will identify the potential of a bacterial protein, termed GAPDH, as a target for control.
Interaction Of Group A Streptococci With Intracellular Innate Immune Defence
Funder
National Health and Medical Research Council
Funding Amount
$824,252.00
Summary
The pathogenic bacterium group A streptococcus (GAS) is estimated to cause ~700 million cases of self-limited throat or skin infection each year worldwide. GAS infections result in over 600,000 human deaths. This disease burden places GAS in the “top 10” causes of human infectious disease deaths worldwide. We have discovered a hitherto unknown mechanism by which GAS subvert the human immune system. An improved understanding of this mechanism will lead to novel ways to combat GAS infections.
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.
Preclinical Studies Of Group A Streptococcal Vaccine Candidates
Funder
National Health and Medical Research Council
Funding Amount
$532,492.00
Summary
Group A streptococcus causes 520,000 deaths each year. A safe and effective vaccine is not commercially available. We have identified 2 new protective candidate antigens, and we seek to undertake critical preclinical studies to provide further proof-of-concept data. This work will underpin commercial decisions by our industry partner (Wyeth) leading to human trials and the development of a safe group A streptococcal vaccine for human use.
Investigating The Antimicrobial Activity Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Streptococcus pneumoniae is a human-only bacterium that is responsible for killing more than one million people every year. This project will analyse how the human immune system fights this bacterium, and subsequently, how the bacteria manages to subvert these attacks and survive in the human host. This will provide crucial information for developing new drugs against this pathogen, in an attempt to combat the ever-increasing problem of antibiotic resistance.
Integrated Bacterial Genomics And Virulence Analysis Of Uropathogenic Streptococcus Agalactiae
Funder
National Health and Medical Research Council
Funding Amount
$747,457.00
Summary
Urinary tract infections (UTI), which start as a bladder infection and often evolve to encompass the kidneys, are among the most common infectious diseases in humans. Streptococcus agalactiae is an important cause of gram-positive bacterial UTI. We will study the genomes and functions of specific genes in reference strains of this bacterium isolated from patients with different forms of infection to elucidate how bacterial genes and virulence factors contribute to these types of infections.
Zinc As An Antimicrobial Agent And Its Effect On The Pathogenesis Of Group A Streptococcus
Funder
National Health and Medical Research Council
Funding Amount
$352,359.00
Summary
This proposal focuses on Group A Streptococcus (GAS), a human pathogen estimated to cause 600,000 human deaths per year. We have shown that the host immune system uses zinc as an antibacterial agent and that GAS has processes that protect against zinc overload. We will determine the way in which zinc mobilization controls GAS infection and how GAS responds to to an increase in zinc concentration. The results will provide new insights into zinc’s role in protection against bacterial infections.