Systems-level Characterisation And Therapeutic Targeting Of Small RNAs In Acinetobacter Baumannii Disease
Funder
National Health and Medical Research Council
Funding Amount
$581,990.00
Summary
This proposal aims to understand how a superbug that causes severe infections in hospitalised patients worldwide and is known to be resistant to almost all available antibiotics, causes disease. We then plan on using this information to guide the development of a new type of therapy to treat this severe infection.
Understanding The Contribution Of SRNAs To Antibiotic Resistance In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$587,424.00
Summary
Golden Staph is a major problem in Australian hospitals. This project will use cutting edge technology to investigate how Golden Staph responds to and resists antibiotics used to treat human infections, leading to new strategies for the prevention and treatment of antibiotic resistant bacteria.
Non-coding RNA Regulation Of Virulence In Enterohaemorrhagic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$389,313.00
Summary
Shiga toxins cause potentially fatal haemolytic uremic syndrome (HUS) and are transferred between bacterial pathogens by bacteriophage (bacterial viruses). We have recently found that the Shiga toxin encoding bacteriophage encodes an unusually large number of non-coding RNAs (RNA regulators of gene expression). This Project aims to understand how these RNA regulators benefit the Shiga toxin bacteriophage and use this knowledge to develop interventions that will prevent expression of the toxin.
Antibiotic Tolerance And Small RNA Networks In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$521,559.00
Summary
Treatment of MRSA is restricted to last line antibiotics and treatment failure is associated with an intermediate tolerance to vancomycin. Regulatory molecules termed small RNA mediate responses to antibiotic challenge but their functions are poorly understood. This proposal will profile sRNA function to understand how they adapt S. aureus to antibiotic challenge. A molecular understanding of vancomycin-tolerance will inform development of diagnostics and treatment strategies.
Targeting Nucleic Acid Synthesis And Cell Division In Gram-negative Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$966,800.00
Summary
Some bacteria like Acinetobacter species cause infections in hospitals that are difficult to treat because they have acquired resistance to most antibiotics. This project will combine the complementary expertise of five research groups to develop knowledge of, and how to block, three essential processes in these worrying pathogenic species: copying of DNA, RNA synthesis, and cell division. This promises to lead to development of new antibacterial therapies.
Targeting Lagging Strand DNA Replication In Model And Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$590,426.00
Summary
An increasing concern is the growing number of hospital acquired infections that cannot be treated effectively with antibiotics because the bacteria that cause them are resistant to drug treatments. This project will develop our basic understanding of how DNA is copied in bacteria that are about to reproduce themselves, and we will use this knowledge to discover ways to stop them from copying their DNA, thus killing them. This will provide the foundation for development of new antibiotics.
Molecular Genetics And Evolution Of Antibiotic Resistant Staphylococci
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Potentially life-threatening infections caused by Staphylococcus aureus bacteria, commonly known as Golden Staph, often arise as complications in patients within hospitals. These infections compromise the health of the patient and jeopardise their recovery from the condition for which they were initially admitted, which significantly increases healthcare costs. Golden Staph is a major cause of hospital-acquired infections in Australia and globally. The problem is largely due to the presence in h ....Potentially life-threatening infections caused by Staphylococcus aureus bacteria, commonly known as Golden Staph, often arise as complications in patients within hospitals. These infections compromise the health of the patient and jeopardise their recovery from the condition for which they were initially admitted, which significantly increases healthcare costs. Golden Staph is a major cause of hospital-acquired infections in Australia and globally. The problem is largely due to the presence in hospitals of strains that are resistant to most clinically-useful antibiotics and are therefore very difficult to eradicate; the recent isolation of strains highly-resistant to one of the last resort anti-staphylococcal antibiotics, vancomycin, is particularly worrying. The emergence of these multiresistant strains is primarily attributable to the acquisition of pre-existing resistance determinants by cell-to-cell gene transfer, a process in which plasmids, extra-chromosomal DNA elements, play a prominent role. Staphylococcal multiresistance plasmids carry genes that can confer resistance to up to 20 antimicrobial agents and are themselves capable of transfer between bacterial cells. In this project, we will define the molecular mechanisms by which staphylococcal multiresistance plasmids efficiently replicate in the host cell and are stably maintained in growing bacterial populations or when acquired by a new host after transfer; such mechanisms may well provide novel drug targets. The results will also lead to the development of improved methods for the characterisation of clinical strains and the monitoring of antibiotic resistance, and will be of broad relevance to the problem of antimicrobial resistance in bacterial pathogens. Most importantly, the application of knowledge arising from these studies to the design and implementation of rational antibiotic usage policies has the potential to extend the efficacy of existing and future anti-staphylococcal therapies.Read moreRead less