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 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.
Molecular Mechanisms Of Plasmid Maintenance In Multiply-resistant Staphylococci
Funder
National Health and Medical Research Council
Funding Amount
$543,778.00
Summary
Serious 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 t ....Serious 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, as is the emergence of resistant strains that cause infections in the wider community. 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 multiresistance plasmids efficiently replicate in the host cell and are stably maintained in bacterial populations. This information will identify targets for agents that can promote the loss of plasmids and hence combat the development of resistance; the activity of one type of agent will be determined in this project. The application of knowledge arising from these studies to has the potential to extend the efficacy of existing and future antimicrobial therapies.Read moreRead less
Functional Biology Of Large Serine Recombinases From Mobile Antibiotic Resistance Elements
Funder
National Health and Medical Research Council
Funding Amount
$436,328.00
Summary
In recent years there has been increasing concern about the emergence of multiply antibiotic resistant strains of many common bacterial pathogens. The development of multiple resistance phenotypes has already led to compromises in the ability to successfully treat infected patients and to increased treatment costs. The emergence of these resistant bacteria is the result of excessive or inappropriate use of antibiotics and the ability of antibiotic resistance genes to be transferred from resistan ....In recent years there has been increasing concern about the emergence of multiply antibiotic resistant strains of many common bacterial pathogens. The development of multiple resistance phenotypes has already led to compromises in the ability to successfully treat infected patients and to increased treatment costs. The emergence of these resistant bacteria is the result of excessive or inappropriate use of antibiotics and the ability of antibiotic resistance genes to be transferred from resistant to susceptible bacteria, either within or between bacterial species. The movement of resistance elements that are integrated into the bacterial genome often involves their excision from their existing site and their subsequent integration into another site in the same or a different genome. This project centres on the analysis of this process in resistant bacteria that cause major disease problems in our hospitals. The research project will focus on MRSA (Multiply Resistant Staphylococcus aureus) which has been a serious problem in our hospitals for many years, and Clostridium difficile, an emerging pathogen of increasing importance and which causes a very serious and chronic form of colitis in hospital patients. By studying the biochemical processes by which enzymes called recombinases excise and subsequently integrate antibiotic resistance elements from these bacteria and by determining the three dimensional structure of such enzymes we aim to determine the mechanism of action of members of this important enzyme family. The major outcomes of the project will be an increased understanding of one of the major processes by which antibiotic resistance determinants can spread both within and between bacterial pathogens of importance in the hospital environment. These studies will contribute towards the development of improved methods for controlling the spread of resistant pathogens and resistance genes in the hospital environment, with concomitant benefits to human health.Read moreRead less
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.
Beta-lactamase Mediated Antibiotic Resistance In Gram-negative Pathogens: How Does Genotype Relate To Phenotype?
Funder
National Health and Medical Research Council
Funding Amount
$397,869.00
Summary
Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expressio ....Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expression of an enzyme called a beta-lactamase. This enzyme breaks down the penicillin. Beta-lactamase enzymes come in many different varieties, and new varieties appear quite frequently. Remarkably, when new kinds of penicillin are invented to circumvent resistance, the appearance of new beta-lactamases that can break down these new penicillins follows shortly thereafter. The objectives of our research are twofold. Firstly, it is now clear that the relationship between the beta-lactamase genes in a bacterium and the resulting pattern of resistance can be very complex. It can involve both the broad nature of the genes, the numbers of duplicates of the genes inside the cell, and very minor changes to the gene sequences. We will probe the relationship between the gene and resistance so as to understand it at a deeper level. Secondly, we will use this information to develop very efficient and cost affective methods for keeping track of the spread of the different varieties of beta-lactamase genes. These methods will be designed to be carried out on real-time PCR machines. These high-tech devices are general purpose gene analyzers that can carry out many different kinds of genetic assay. They are rapidly becoming ubiquitous in clinical microbiology laboratories. The use of these methods will provide much hard information that will be used to minimise the dissemination of antibiotic resistance.Read moreRead less
A New Class Of Inhibitors For The Treatment Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$720,691.00
Summary
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, with 1.3 million deaths annually. Some strains of the TB bacterium are resistant to all available drugs. We have identified novel chemical structures that display potent and specific activity against pathogenic mycobacteria. In this proposal we will develop optimised derivatives with more potent activity against mycobacteria, assess their stability and toxicity and determine their mode of action.
Molecular Epidemiology Of Antibiotic Resistant Salmonella Enterica Strains Causing Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$493,767.00
Summary
Salmonella infections are responsible for a substantial proportion of reported food poisoning cases caused by bacteria and many of these infections are due to antibiotic resistant strains. Infections caused by antibiotic resistant organisms are hard to treat and generally more severe, of longer duration, and result in longer hospital stays. These strains are mostly acquired from foods, e.g. meats, dairy products, poultry, eggs, and other contaminated food products but can also be derived from ot ....Salmonella infections are responsible for a substantial proportion of reported food poisoning cases caused by bacteria and many of these infections are due to antibiotic resistant strains. Infections caused by antibiotic resistant organisms are hard to treat and generally more severe, of longer duration, and result in longer hospital stays. These strains are mostly acquired from foods, e.g. meats, dairy products, poultry, eggs, and other contaminated food products but can also be derived from other sources. Salmonella strains harboured by food-producing animals are the source of most of the food contamination.Tracing the source of individual resistant strains is essential for eradication and as there are many Salmonella types, some of which are found associated only with specific animals or birds, accurate identification is needed. The proposed work will make this process more accurate by using molecular techniques to unequivocally establish suspected connections and reveal further ones that are difficult to discern using current data and methods. This should decrease the number of infections due to resistant strains.Read moreRead less