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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
Characterisation Of Community Methicillin-resistant Staphylococcus Aureus And Their Control In Remote Communities
Funder
National Health and Medical Research Council
Funding Amount
$300,777.00
Summary
Before the introduction of antibiotics Staphylococcus aureus, the golden staph , was the major cause of infections in hospitals. Although the introduction of antibiotics helped control the organism it has gradually acquired resistance until strains have emerged which can only be treated with vancomycin. Consequently staphs have again emerged as a major hospital pathogen. The emergence of these multiply resistant strains corresponded to them acquiring methicillin resistance and consequently they ....Before the introduction of antibiotics Staphylococcus aureus, the golden staph , was the major cause of infections in hospitals. Although the introduction of antibiotics helped control the organism it has gradually acquired resistance until strains have emerged which can only be treated with vancomycin. Consequently staphs have again emerged as a major hospital pathogen. The emergence of these multiply resistant strains corresponded to them acquiring methicillin resistance and consequently they have come to be known as methicillin-resistant Staphylococcus aureus or MRSA. Soon after the emergence of MRSA the hospitals of Western Australia (WA) developed a policy to prevent introduced MRSA from becoming established in its hospitals. Although this has been successful the policy is now under threat with the emergence of MRSA in remote WA Aboriginal communities. Aboriginals in these communities have a large number of infections which are usually treated empirically. This can result in the selection of antibiotic resistant bacteria if they are present. Consequently, it is planned to regularly screen Aboriginal communities which are known to have a high prevalence of MRSA and recommend antibiotic prescribing which will not select for any resistant staphylococci carried by a person. This is possible because the community MRSA are still susceptible to some anti-staphylococcal drugs. If this program is shown to reduce the prevalence of MRSA in the communities then the program will be extended to other communities. Community MRSA are now being reported from other Australian states and it is planned to study these to see if they are related to the WA strains. The community isolates will be studied to assess their potential to acquire additional antibiotic resistances. As some strains are known to be more of a threat to hospitals than others methods will be investigated to develop rapid methods for detecting them.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