Curing Antibiotic Resistance: Probiotic Plasmids And Microbial Husbandry In The Enterobacteriaceae
Funder
National Health and Medical Research Council
Funding Amount
$560,832.00
Summary
The most troublesome emerging antibiotic resistance is coming in the form of addictive and promiscuous 'pest' plasmids, carrying dangerous genes that defeat antibiotics used for the most severe infections. We currently manage this problem by isolating infected patients and trying to design new antibiotics. Our approach eradicates these plasmids and renders the host bacterium antibiotic susceptible again, thereby restoring the natural ecology in animals and potentially in humans.
Molecular Basis For Conjugative Transfer Of Antibiotic Resistance Genes In Gram Positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$872,660.00
Summary
There has been growing concern about the increasing level of antibiotic resistance in bacterial pathogens. We will use a model genetic element to determine the mechanism by which an important class of pathogenic bacteria can acquire new resistance genes by a process known as horizontal gene transfer. The project will significantly enhance our understanding of how major hospital and community acquired pathogenic bacteria can rapidly evolve to become resistant to different antimicrobial agents.
Antibiotic Resistance And The Ecological Effects Of Selective Decontamination Of The Digestive Tract In Intensive Care Units
Funder
National Health and Medical Research Council
Funding Amount
$901,396.00
Summary
We will study patients within a large trial of gut decontamination, in which antibiotics are given in advance to reduce the risk of infection. Specifically, we will determine whether there is any increased antibiotic resistance and even biodiversity loss, as some fear. This is a one-off chance to provide essential data that can help us design better national policies for antibiotic resistance control and a true personalised medicine approach to resistance and infection in ICU.
Mechanisms Of Stable Gene Inheritance In Multiresistant Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$620,357.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections in Australia and around the world. The bacteria have mechanisms that cause efficient inheritance of resistance genes, even when antibiotics are no longer being used. This project will elucidate key aspects of such mechanisms so that treatments can be devised that interfere with the development and maintenance of resistance.
Horizontal And Vertical Transmission Mechanisms Of Staphylococcus Aureus Multiresistance Plasmids
Funder
National Health and Medical Research Council
Funding Amount
$408,993.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections. The bacteria have mechanisms that cause efficient transmission of resistance genes to their offspring as well as to other strains. This project aims to elucidate key features of these mechanisms so that treatments can be devised that disrupt the maintenance and transfer of resistance, so as to prolong the effectiveness of antibiotics.
Redefining Antibiotic Resistance Plasmid Transfer In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$735,585.00
Summary
Multidrug-resistant Golden Staph bacteria are a major health problem. Resistance develops rapidly because bacteria efficiently acquire/share resistance genes. Our discoveries suggest DNA transfer mechanisms are far more diverse and widespread than previously expected and this has wide-reaching implications for numerous pathogenic organisms. This project aims to define the prevalence and key features of each mechanism so treatments can be devised to disrupt the evolution and spread of resistance.
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
Molecular Genetics And Evolution Of Antibiotic Resistant Staphylococci
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
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. Hospital-acquired infections caused by Golden Staph are a major problem in Australia and globally. The problem is largely due to the pre ....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. Hospital-acquired infections caused by Golden Staph are a major problem in Australia and globally. The problem is largely due to the presence in hospitals of strains that have become resistant to most clinically-useful antibiotics and are therefore very difficult to eradicate. This research project will reveal detailed information about strains of Golden Staph that are currently prevalent in hospitals in Australia, USA, Europe, and South East Asia. It will also provide important insights into the mechanisms that enable this organism to become resistant so readily, and identify factors that promote the development of resistant strains. The results of this research project will lead to improved methods for the characterisation of clinical strains and the monitoring of antibiotic resistance. The findings will also be of relevance to other types of antibiotic resistant bacteria. Most importantly, the application of knowledge arising from these studies has potential to minimise the emergence of strains that are even more resistant, thereby extending the effectiveness of existing and future antibiotics. The design and implementation of strategies to limit the proliferation of resistant bacteria are essential if we are to avoid a scenario similar to that prior to the introduction of antibiotics, when serious infectious diseases were often untreatable.Read moreRead less
This program directly addresses the major threat of antimicrobial resistance , bringing together the power of modern genomics and the promise of novel positive therapies to eradicate AMR organisms and AMR genes from individuals at risk from severe infection.