Antibiotic Resistance And Multiple Antibiotic Resistance In Human Commensal Escherichia Coli In Australia
Funder
National Health and Medical Research Council
Funding Amount
$509,202.00
Summary
Antibiotic resistance, particularly resistance to all or nearly all of the antibiotics available for treatment is now very common and impacts heavily on the treatment of bacterial infections. This project will track resistance genes in reservoirs where antibiotic resistance genes may be present in high concentrations as these are a likely source of the resistance genes in disease-causing bacteria. One such reservoir, the bacteria in the intestines of healthy humans will be examined.
Novel Therapeutic Strategy Against Multidrug-resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$349,823.00
Summary
In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the l ....In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the last 40-50 years, has been 'taken off the shelf' and is now being used as a last line of defence to treat people with infections caused by these bacteria. Clearly, doctors and their infected patients will be in an even more precarious position than currently exists if resistance to colistin increases. We have discovered a novel therapeutic strategy that is able to reverse colistin resistance in P. aeruginosa. The studies proposed in this project will investigate this novel strategy across a range of multidrug-resistant bacteria and provide the information essential for rational use in patients. We propose that such a novel therapeutic strategy will provide a powerful weapon for the war on these 'superbugs'.Read moreRead less
Molecular Mechanisms Of Low-level Vancomycin Resistance In Clinical Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$437,916.00
Summary
The common bacteria Staphylococcus aureus causes many infections in humans, and is becoming more resistant to antibiotic treatments, especially in hospitals. This project will determine how this bacteria is developing resistance to some of our last available antibiotics. This will provide an important basis for detecting and preventing this antibiotic resistance problem in future.
Understanding Complex Genomic And Biochemical Landscapes In Human Health Microbiology
Funder
National Health and Medical Research Council
Funding Amount
$2,210,520.00
Summary
There is increasing awareness of the critical roles microbes play in health. The microbes in our gut produce chemicals that control everything from our moods, to food metabolism and immune system function. In this proposal leading-edge technologies from the disciplines of microbiology, genomics, mass-spectrometry and computational biology will be used to reveal for the first time how and why these chemicals are produced by microbes in complex systems that are important for human health.
Metallo-beta-lactamases: Predicting And Combating Antibiotic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$530,424.00
Summary
The increase of drug-resistant bacterial pathogens has become a major global health concern. Many pathogens employ a special enzyme, named metallo-beta-lactamase (MBL), to degrade antibiotics such as penicillin. No clinically useful inhibitors of this enzyme are available. We will use sophisticated techniques to predict and combat drug resistance of the MBL from Klebsiella pneumoniae, a pathogen associated in particular with hospital-acquired infections such as urinary tract infections.
Nucleic Acid Synthesis And Cell Division In Model Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$781,345.00
Summary
The rise of antibiotic resistance, particularly in hospitals, over recent years represents a huge financial burden on the health system, in addition to the personal costs to the patient infected. Over the last 60 years, we have become accustomed to the availability of antibiotics that can effectively treat most, if not all, bacterial infections. Today, this is not the case, and some bacteria in hospitals are resistant to all therapeutically useful antibiotics. The costs of drug development are v ....The rise of antibiotic resistance, particularly in hospitals, over recent years represents a huge financial burden on the health system, in addition to the personal costs to the patient infected. Over the last 60 years, we have become accustomed to the availability of antibiotics that can effectively treat most, if not all, bacterial infections. Today, this is not the case, and some bacteria in hospitals are resistant to all therapeutically useful antibiotics. The costs of drug development are very considerable; from the financial perspective of a pharmaceutical company, the de novo development of new antibiotics is not attractive because they are drugs that are only used for a short period. Recoupment of development costs takes a long time. As a result, very few new antibiotics are currently in development, and many of the newer ones are the result of academic efforts and subsequent formation of spin-out companies that develop new drugs through to phase 1 trials. The need for new, and effective, antibiotic therapies is pressing. We propose to identify and validate the use of key essential biological processes as targets for the development of new antimicrobial agents in two important hospital pathogens. Staphylococcus aureus is a well known and established pathogen that is the number one cause of hospital acquired (nosocomial) infections. Acinetobacter sp. is a relatively new problem in nosocomial infections, but is growing in importance due to the startling rate at which it is able to acquire resistance to antibiotics. In both organisms, we intend to target essential protein-protein interactions involved in DNA replication (duplication of genetic material), transcription (production of a genetic message), and cell division. The targeting of protein-protein interactions, rather than the enzymic activity of a protein provides a novel and unexploited avenue for antibacterial development with great potential for success.Read moreRead less
Interactions Between Integrative Genomic Islands And Plasmids; Role In The Spread And Loss Of Antibiotic Resistance And Pathogenicity Determinants
Funder
National Health and Medical Research Council
Funding Amount
$776,465.00
Summary
Mobile elements that integrate into bacterial chromosomes at a specific site contribute pathogenicity and antibiotic resistance determinants to their bacterial host but only a few are able to move themselves into new hosts. Some plasmids and some elements can help certain others. In this project, genetic approaches will be used to investigate how plasmids and integrative elements help one another move into a new bacterium or compete with one another to stay in the same cell.
Eradication Of High-risk Bacterial Clones Using Bacteriophages
Funder
National Health and Medical Research Council
Funding Amount
$685,070.00
Summary
Nature offers remedies to the spread of dangerous antibiotic resistant bacteria in the form of predatory viruses (bacteriophages). In this project, we will define optimal mixtures of these for killing problem bacterial types, the mechanisms by which bacterial resistance develops, the best approach to identifying susceptible bacteria and to using these viruses to eradicate them, and we will test a carefully optimised bacteriophage therapy in humans colonised by the dangerous E. coli ST131 strain.
Prevention And Treatment Of Bone Infection With CSA-90
Funder
National Health and Medical Research Council
Funding Amount
$350,983.00
Summary
Bone infections are a major challenge to treat, especially with the rise of drug resistant “superbugs”. We have access to a new agent, CSA-90, that has dual properties of being anti-microbial (antibiotic) and helps encourage bone growth. This project aims to expand upon our prior research and test CSA-90 for the treatment of chronic bone infections. We will also look at applying this technology to joint replacements and this drug may be particularly useful for coating orthopaedic implants.