Molecular Typing Of Salmonella Enterica Serovar Typhimurium
Funder
National Health and Medical Research Council
Funding Amount
$272,545.00
Summary
Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subd ....Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subdivide Typhimurium is phage typing, which is done only in major laboratories (2 in Australia). Phage typing is based on lysis patterns of a test isolate to a set of 34 phages. Phage typing has played a crucial role in tracking the organism, for example the emergence of a multidrug resistance new type (DT204c) in UK and US. The technique is simple but the problem is that reactions vary with slight change in conditions and scoring the reaction results is very subjective. We propose to replace the typing system with one based on the DNA method PCR, so it will be simple, fast and accurate. We will use a DNA fingerprinting technique called AFLP (amplified fragment length polymorphism) to find markers (DNA segments) that are specific to phage types and design PCR assays based on the markers we find. Such a typing system will retain the essence of phage typing by providing continuity of the valuable epidemiological database on phage types. Further the typing system could easily be expanded to accommodate any new types by finding more markers while the current phage typing system is very difficult to expand (last done in 1977 and is behind in our needs). This project will establish a general approach for designing typing systems based on molecular biology for other pathogens and could have a major impact on the surveillance of bacterial infections in the 21st century.Read moreRead less
Tissue Specific T Cells Mediate Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$1,253,980.00
Summary
T cells are immune cells that create dangerous and fatal drug allergies affecting the skin. An individual’s genetic makeup only partially explains predisposition to these reactions, we believe the missing link is contained in immune signatures specific to the skin. We aim to identify drug-specific T cells in the skin and develop a sensitive test to screen for rare, dangerous T cells in the blood. This will enable prediction and prevention of severe drug allergy and development of safer drugs.
Characterisation Of Community Methicillin-resistant Staphylococcus Aureus And Their Control In Remote Communities
Funder
National Health and Medical Research Council
Funding Amount
$300,777.00
Summary
Before the introduction of antibiotics Staphylococcus aureus, the golden staph , was the major cause of infections in hospitals. Although the introduction of antibiotics helped control the organism it has gradually acquired resistance until strains have emerged which can only be treated with vancomycin. Consequently staphs have again emerged as a major hospital pathogen. The emergence of these multiply resistant strains corresponded to them acquiring methicillin resistance and consequently they ....Before the introduction of antibiotics Staphylococcus aureus, the golden staph , was the major cause of infections in hospitals. Although the introduction of antibiotics helped control the organism it has gradually acquired resistance until strains have emerged which can only be treated with vancomycin. Consequently staphs have again emerged as a major hospital pathogen. The emergence of these multiply resistant strains corresponded to them acquiring methicillin resistance and consequently they have come to be known as methicillin-resistant Staphylococcus aureus or MRSA. Soon after the emergence of MRSA the hospitals of Western Australia (WA) developed a policy to prevent introduced MRSA from becoming established in its hospitals. Although this has been successful the policy is now under threat with the emergence of MRSA in remote WA Aboriginal communities. Aboriginals in these communities have a large number of infections which are usually treated empirically. This can result in the selection of antibiotic resistant bacteria if they are present. Consequently, it is planned to regularly screen Aboriginal communities which are known to have a high prevalence of MRSA and recommend antibiotic prescribing which will not select for any resistant staphylococci carried by a person. This is possible because the community MRSA are still susceptible to some anti-staphylococcal drugs. If this program is shown to reduce the prevalence of MRSA in the communities then the program will be extended to other communities. Community MRSA are now being reported from other Australian states and it is planned to study these to see if they are related to the WA strains. The community isolates will be studied to assess their potential to acquire additional antibiotic resistances. As some strains are known to be more of a threat to hospitals than others methods will be investigated to develop rapid methods for detecting them.Read moreRead less
Methylation-sensitive T Cell Genes And Childhood Food Allergy.
Funder
National Health and Medical Research Council
Funding Amount
$461,232.00
Summary
Australia has the highest reported prevalence food allergy in the world. Despite this, little is known about how allergy develops. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of food challenge proven food allergy with assessment of immune functioning & cutting edge genomics, to extensively characterise the pathways leading to food allergy in children.
Identification And Analysis Of Novel Replication Initiation Factors In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$311,789.00
Summary
Multi-drug resistant Golden staph is a serious medical problem around the world because strains are often resistant to commonly used treatments; new drugs are therefore urgently required. DNA replication is a fundamental process that is essential for the survival of all cellular organisms. This project aims to identify and characterise novel factors involved in DNA replication in Golden staph, which represent potential drug targets.
Plasmids are additional mini-chromosomes carried by many bacteria. They carry information that enables their hosts to prosper in otherwise hostile environments. Plasmids spread rapidly between bacteria, efficiently disseminating plasmid-borne information throughout bacterial populations. Many plasmids carry information that increases the virulence of their host. The emergence of multi-drug resistant bacteria and the rapid spread of the information enabling bacteria to withstand most antibiotics ....Plasmids are additional mini-chromosomes carried by many bacteria. They carry information that enables their hosts to prosper in otherwise hostile environments. Plasmids spread rapidly between bacteria, efficiently disseminating plasmid-borne information throughout bacterial populations. Many plasmids carry information that increases the virulence of their host. The emergence of multi-drug resistant bacteria and the rapid spread of the information enabling bacteria to withstand most antibiotics available today, were mediated by plasmids. Plasmids also carry information that ensures their own survival. Consequently, their hosts retain the plasmids even when it is no longer beneficial for them to do so. For example, plasmids mediating resistance to antibiotics are not lost when bacterial hosts are grown in the absence of those antibiotics. That is because plasmids have control systems, which ensure both that replication of the plasmid keeps pace with that of its host, and that the plasmid does not produce so many copies of itself that it overwhelms its host or places it at a competitive disadvantage amongst other bacteria. This project examines the intricate regulatory system that enables two groups of antibiotic-resistance plasmids to ensure that, on average, each plasmid molecule is replicated once per bacterial cell cycle. This system uses a tertiary RNA structure as a molecular switch, an antisense RNA as the regulator of this switch, and a protein that interacts with DNA sequences on the plasmid and with a bacterial protein, to initiate replication. Information gained from studies of plasmid systems is essential to the development of treatments for the elimination of antibiotic-resistance and virulence-contributing plasmids from populations of pathogenic bacteria. Antisense RNAs are not only a powerful research tool, but are also being developed for therapeutic use. Understanding how these RNAs interact with their targets will increase their effectiveness.Read moreRead less