Role Of Novel Mobile Elements In The Infiltration Of Antibiotic Resistance Genes Into Clinical Isolates.
Funder
National Health and Medical Research Council
Funding Amount
$421,650.00
Summary
Bacteria have a remarkable ability to capture and spread antibiotic resistance genes. This phenomenon is a particular problem in our hospitals and in the community as multi-drug resistant pathogenic organisms have been selected over time as a result of the use of antibitoics. Moreover the incidence of resistance appears to be on the increase. Once resistant strains appear they can greatly complicate the treatment of infections and the eradication of such pathogens from a hospital is both difficu ....Bacteria have a remarkable ability to capture and spread antibiotic resistance genes. This phenomenon is a particular problem in our hospitals and in the community as multi-drug resistant pathogenic organisms have been selected over time as a result of the use of antibitoics. Moreover the incidence of resistance appears to be on the increase. Once resistant strains appear they can greatly complicate the treatment of infections and the eradication of such pathogens from a hospital is both difficult and costly. We have been working on the problem of how antibiotic resistance genes are spread for a number of years and have identified a novel genetic element that can capture resistance genes by a process of site-specific recombination. This element, the integron, is common in mutli-drug resistant clinical isolates. To be captured by an integron, an antibiotic resistance gene has to be part of a mobile element known as a gene cassette. Although the application of antibiotics acts to amplify pathogens that are resistant and favours their persistance in hospitals, it is generally recognized that neither the gene cassette nor the drug resistance gene evolve in the hospital. Rather, these genes make their way into human pathogens from bacteria that normally reside in other environments, for example soil or water. In this project, we will investigate one route by which drug resistance genes and integrons might find their way into clinically relevant strains and what the sources of the resistance genes and gene cassettes might be. A greater understanding of these processes will help in developing strategies to limit the spread of drug resistant bacteria into and around hospitals.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
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
Plasmids are additional mini-chromosomes carried by many bacteria. They carry information that enables their hosts to prosper in otherwise hostile environments. Plasmids spread rapidly between bacteria, efficiently disseminating plasmid-borne information throughout bacterial populations. Many plasmids carry information that increases the virulence of their host. The emergence of multi-drug resistant bacteria and the rapid spread of the information enabling bacteria to withstand most antibiotics ....Plasmids are additional mini-chromosomes carried by many bacteria. They carry information that enables their hosts to prosper in otherwise hostile environments. Plasmids spread rapidly between bacteria, efficiently disseminating plasmid-borne information throughout bacterial populations. Many plasmids carry information that increases the virulence of their host. The emergence of multi-drug resistant bacteria and the rapid spread of the information enabling bacteria to withstand most antibiotics available today, were mediated by plasmids. Plasmids also carry information that ensures their own survival. Consequently, their hosts retain the plasmids even when it is no longer beneficial for them to do so. For example, plasmids mediating resistance to antibiotics are not lost when bacterial hosts are grown in the absence of those antibiotics. That is because plasmids have control systems, which ensure both that replication of the plasmid keeps pace with that of its host, and that the plasmid does not produce so many copies of itself that it overwhelms its host or places it at a competitive disadvantage amongst other bacteria. This project examines the intricate regulatory system that enables two groups of antibiotic-resistance plasmids to ensure that, on average, each plasmid molecule is replicated once per bacterial cell cycle. This system uses a tertiary RNA structure as a molecular switch, an antisense RNA as the regulator of this switch, and a protein that interacts with DNA sequences on the plasmid and with a bacterial protein, to initiate replication. Information gained from studies of plasmid systems is essential to the development of treatments for the elimination of antibiotic-resistance and virulence-contributing plasmids from populations of pathogenic bacteria. Antisense RNAs are not only a powerful research tool, but are also being developed for therapeutic use. Understanding how these RNAs interact with their targets will increase their effectiveness.Read moreRead less