Structure, Formation And Evolution Of Multiple Antibiotic And Mercury Resistance Regions In Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$550,500.00
Summary
Antibiotic resistance and particularly resistance to several different antibiotics simultaneously is becoming alarmingly common in bacteria that cause infectious diseases in humans and animals. New antibiotics are proving slow to appear and the most obvious way to increase the effectiveness and the useful lifetime of existing antibiotics is though attempting to reduce the prevalence of resistant bacteria. This can only be done using good surveillance that allows the places where resistant bacter ....Antibiotic resistance and particularly resistance to several different antibiotics simultaneously is becoming alarmingly common in bacteria that cause infectious diseases in humans and animals. New antibiotics are proving slow to appear and the most obvious way to increase the effectiveness and the useful lifetime of existing antibiotics is though attempting to reduce the prevalence of resistant bacteria. This can only be done using good surveillance that allows the places where resistant bacteria and resistance genes are present in large numbers, e.g. in food-production animals, in hospitals, in the human gut or in the environment, to be identified. Very little data of this type is available internationally and even less for the Australian situation. Using recent knowledge of resistance genes and modern molecular techniques the work will identify which resistance genes and combinations of resistance genes confering resistance to antibbiotics used either in the clinic or administered to food-producing animals or both are found in Australian isolates. By examining multiply antibiotic resistant isolates from these two and other sources the flow of resistance genes and resistant bacteria between these two reservoirs will be tracked accurately. This will allow the sources relevant to difficult to treat or untreatable infections acquired in the hospital setting to be identified and appropriate action taken.Read moreRead less
Antibiotic resistance increases mortality and costs in the Intensive Care Unit (ICU), but the impact of antibiotic therapy has not been adequately studied. We propose to characterise the behaviour of key elements of the bacterial microflora (resistant bacteria and major resistance genes) in response to antibiotics. We have developed new rapid diagnostics to harness these data and this proposal has the potential to greatly improve diagnostic speed and accuracy and thus clinical outcomes.
Antimicrobial Stewardship - Establishing Effective Programs For Australian Hospitals
Funder
National Health and Medical Research Council
Funding Amount
$1,232,361.00
Summary
This project will examine strategies to improve the use of antimicrobial drugs in Australian hospitals. It will evaluate the impact of antimicrobial stewardship programs on antibiotic prescribing practices in Victorian tertiary hospitals and determine the organisational factors associated with success. It will also examine the needs, and establish models for antimicrobial stewardship beyond the tertiary hospital setting, in private hospitals, small metropolitan and rural hospitals.
Plasmids are extra mini-chromosomes that are present in many bacteria. They carry information that enables their hosts to survive and prosper in hostile environments. Plasmids are able to spread rapidly between bacteria, ensuring that the information they carry is rapidly disseminated throughout bacterial populations. Many plasmids carry information that increases the virulence of their host bacteria, because it adds to their repertoire of toxins and other adjuncts to invasiveness and colonisati ....Plasmids are extra mini-chromosomes that are present in many bacteria. They carry information that enables their hosts to survive and prosper in hostile environments. Plasmids are able to spread rapidly between bacteria, ensuring that the information they carry is rapidly disseminated throughout bacterial populations. Many plasmids carry information that increases the virulence of their host bacteria, because it adds to their repertoire of toxins and other adjuncts to invasiveness and colonisation, or enables them to survive in the presence of antibiotics. The emergence of multi-drug resistant bacteria and the rapid spread of the ability of bacteria to withstand most antibiotics available to date were mediated by plasmids. Plasmids also carry information that ensures their own survival. The consequence of this is that their bacterial hosts retain the plasmids, even when it is no longer beneficial to do so. For example, plasmids carrying information for resistance to antibiotics are not lost when their bacterial hosts grow in the absence of antibiotics. This is because plasmids have control systems, which ensure that on the one hand, replication of the plasmid keeps pace with the replication of its host, and on the other hand that the plasmid does not produce so many copies of itself that it overwhelms its host. This project examines the intricate regulatory system that a group of antibiotic-resistance plasmids uses to ensure that on average each plasmid molecule is replicated once per bacterial cell cycle. This system uses an antisense RNA, a tertiary RNA structure (pseudoknot) that acts as a translational switch, and a protein that interacts with different sequences on the plasmid to initiate replication. Detailed knowledge of the processes underlying this complex system is required if we are to develop new treatments that will lead to elimination of antibiotic-resistance and virulence-contributing plasmids from populations of pathogenic bacteria.Read moreRead less
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.
The Epidemiology And Treatment Of Infections Due To Multiresistant Gram Negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$274,946.00
Summary
This fellowship application deals with the treatment of infections due to antibiotic resistant bacteria. The World Economic Forum recently discussed threats to our modern way of life. The highest ranked threats were climate change, terrorism and antibiotic resistance. During this Fellowship, two large clinical trials of treatment strategies for antibiotic resistant bacteria will be supervised by Professor Paterson.
The Development Of Novel Antibacterials Targeting Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$750,546.00
Summary
Clostridium difficile is a bacterium associated with infections in the gut which may result in mild to severe diarrhoea and inflammation of the colon. These infections are an increasing problem for hospitalised patients in the US, the EU and Australia. We have been very successful in the past at developing new drugs to treat external infections caused by resistant strains of bacteria, for example, golden Staph. We now aim to develop our drugs to treat C. difficile infections in the gut.
The rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This pro ....The rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This project is centred on bacteria that cause intestinal diseases and have the potential to transfer genetic information to other bacteria that are present in the intestine. The focus will be on elucidating the mechanism of action of an enzyme encoded by two of these genetic elements. This enzyme is responsible for the movement of these elements from one site in the bacterial genome to another, by a process that is being increasingly recognised as important in antibiotic-resistant disease-causing bacteria. The project will employ the latest tools of molecular biology to determine the function of this enzyme, and its associated genetic elements, at the detailed molecular level. These studies will contribute to our understanding of how these antibiotic resistance elements are transferred within and between different bacterial cells. In the longer term the project will contribute towards the development of improved methods for the control and treatment of infectious diseases.Read moreRead less
Rescuing The Last-line Therapy Colistin Against Gram-negative ‘superbugs’: Increasing The Therapeutic Index By Attenuation Of Nephrotoxicity
Funder
National Health and Medical Research Council
Funding Amount
$498,631.00
Summary
Antibiotic resistance in Gram-negative ‘superbugs’ is presenting a significant global medical challenge. Colistin (polymyxin E) is increasingly used as the last treatment option even though the current use is suboptimal. Simply increasing the daily dose is not an option due to kidney toxicity. This project focuses on a new approach using antioxidants to ameliorate the potential for colistin-induced kidney toxicity, thereby allowing higher doses to achieve adequate bacterial kill in patients.