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DNA Segregation In Multiresistant Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$306,592.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of hospital-acquired, and increasingly community-acquired, infections in Australia and around the world. Bacterial growth depends on the faithful inheritance of genetic material, which is facilitated by active DNA segregation. This project will elucidate key aspects of segregation processes so that treatments can be devised that interfere with the growth of this important pathogen and the development 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 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
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