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
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
A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a ....A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a population some cells will lack genes that others have. Some of these shared genes apart from antibiotic resistance can be a concern and include traits that make some bacteria pathogenic. Thus, two cells of the same species may have very different abilities to cause disease based on what additional genes they carry. Genomics is becoming one of the great scientific revolutions of the 21st century. Over 160 microbial genomes have been sequenced to date and from these studies we have also learned many important things including how some bacteria cause disease. Mobile DNA presents unique challenges to microbial genomics however since different individuals in a species can have many different genes. Thus genomics on even many individuals of a species may miss bacterial genes important to us. Here we will be applying genomics in a way that specifically targets those genes that are shared. This will have many benefits. We will be able to greatly increase our rate of discovery of medically important and other genes in way that is targeted. This approach will allow us to discover these shared genes in a way that is much more cost effective and faster than conventional whole cell genomics. It will also allow us to gain an understanding of how benign bacteria associated with humans may act as reservoirs for passing on harmful genes to bacteria that cause hospital infections.Read moreRead less
Multi-Targeted Inhibition Of An Essential Tetrameric Enzyme From Drug -Resistant Streptococcus Pneumonie.
Funder
National Health and Medical Research Council
Funding Amount
$534,313.00
Summary
Streptococcus pneumoniae is an significant human pathogen which causes several diseases including pneumonia and meningitis. Treatment of infection involves the use of antibiotics such as penecillin, however, resistant strains are now emerging. This project will address the real need to develop new antibiotics targeting this organism. This is essentially a drug discovery project which exploits a novel means to target Streptococcus pneumoniae.
Plasmid Specialisation Modules, Microbial Husbandry And Microbiome Resilience
Funder
National Health and Medical Research Council
Funding Amount
$645,005.00
Summary
The epidemiology of plasmids is chiefly determined by small genetic modules that control their entry to cells, their stability after entry, and their capacity to exclude other related plasmids. Understanding this is important for understanding transmission of antibiotic resistance. It is also essential for our newly proven approach to remove resistance plasmids from bacteria.
Understanding The Complex Relationship Between Host, Pathogen And Antibiotic Factors On Treatment Outcome In Serious Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$380,945.00
Summary
Millions of people still die every year from bacterial infections despite the availability of antibiotics. The same bacterial infection in one person can behave very differently in another person, so infections can range from trivial to life-threatening or fatal. Understanding the relationship between the patient, the infecting bacteria and the antibiotic treatment given will ultimately help to predict and improve outcomes for patients with serious bacterial infections.
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.
Multiple Antibiotic Resistance In An Acinetobacter Baumannii Global Clone
Funder
National Health and Medical Research Council
Funding Amount
$606,580.00
Summary
Antibiotic resistant bacteria that cause infections in hospitals can originate anywhere, then spread world wide. They start off resistant to a few antibiotics, then become resistant to new antibiotics that are introduced to treat them. This project will investigate how resistance to antibiotics was acquired by Acinetobacter baumannii which is now resistant to most antibiotics, and why the old resistance genes are not being lost. This will help track these bacteria moving into and around Australi ....Antibiotic resistant bacteria that cause infections in hospitals can originate anywhere, then spread world wide. They start off resistant to a few antibiotics, then become resistant to new antibiotics that are introduced to treat them. This project will investigate how resistance to antibiotics was acquired by Acinetobacter baumannii which is now resistant to most antibiotics, and why the old resistance genes are not being lost. This will help track these bacteria moving into and around Australia.Read moreRead less
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.