Characterisation Of The Host Response In A Mouse Model Of Staphylococcus Aureus Keratitis.
Funder
National Health and Medical Research Council
Funding Amount
$248,850.00
Summary
Staphylococcus is the most common cause of bacterial eye infections (microbial keratitis) . This ocular infection is associated with severe pain, redness, discharge and frequently results in the loss of vision or blindness. Predisposing factors for this disease include contact lens wear and immunocompromised individuals such as those with HIV, diabetes or aged populations. S. aureus keratitis is difficult to treat using conventional antibiotics as although bacteria may be eliminated, vision loss ....Staphylococcus is the most common cause of bacterial eye infections (microbial keratitis) . This ocular infection is associated with severe pain, redness, discharge and frequently results in the loss of vision or blindness. Predisposing factors for this disease include contact lens wear and immunocompromised individuals such as those with HIV, diabetes or aged populations. S. aureus keratitis is difficult to treat using conventional antibiotics as although bacteria may be eliminated, vision loss may still result from scarring. S. aureus also causes a wide range of hospital associated infections such as pneumonia, endocarditis, bacteremia, wound infections, osteomyelitis and septic arthritis. In recent times strains of S. aureus have emerged which are multi-drug resistant including methicillin resistant S. aureus (MRSA). These may only be treated with the drug Vancomycin. However, vancomycin resistant S. aureus have been reported in both Japan and the USA. Now, the search for new treatments for this bacterium is of vital importance. This project will utilise the novel S.aureus mouse model for keratitis, which we have developed in our laboratories. Our model will enable us to investigate the host responses to bacterial infection. Existing models in the rabbit do not allow such detailed studies due to the lack of existing molecular probes and antibodies. Insights into potential adjunct therapies will also be gained. This research could lead to the development of novel therapeutic measures aimed at manipulating the host response to reduce scarring and consequent blindness. This information may also be important for the development of prophylactic treatments for those patients at high risk, such as diabetics and immunocompromised individuals of developing this disease.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
Do Rapid Detection & Isolation Of Colonised Patients Reduce MRSA Spread? An Epidemiological, Economic & Modelling Study
Funder
National Health and Medical Research Council
Funding Amount
$354,299.00
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) is the antibiotic resistant form of Golden Staph. It is one of the most common causes of hospital acquired infection. Despite the presence of MRSA for more than 40 years in our hospitals, the most efficient ways of controlling it are still debated. Some experts recommend swabbing all high risk patients for MRSA, isolating those found to be carriers it in single rooms or with other carriers and using special precautions, such as gowns and gloves, ....Methicillin-resistant Staphylococcus aureus (MRSA) is the antibiotic resistant form of Golden Staph. It is one of the most common causes of hospital acquired infection. Despite the presence of MRSA for more than 40 years in our hospitals, the most efficient ways of controlling it are still debated. Some experts recommend swabbing all high risk patients for MRSA, isolating those found to be carriers it in single rooms or with other carriers and using special precautions, such as gowns and gloves, when in contact with these patients. One of the problems with this approach is that it takes 2-3 days to detect MRSA from swabs using the usual culture methods in the microbiology laboratory. This means that there are delays in instituting control measures, which may reduce their effectiveness. We plan to test whether use of isolation and special precautions is better than our current practices in preventing the spread of MRSA from patient to patient in the Royal Melbourne Hospital intensive care unit. Patients will be swabbed several times during their admission to see if they are carrying MRSA. We will use new, rapid laboratory methods that can detect MRSA within hours from these patient specimens. This will mean that if patients are found to be carriers, isolation and special precautions can be implemented early. We will compare how many people get MRSA in the time when we are not using any special precautions with how many get it in the time when we are. We are also going to undertake an economic analysis to see whether, even if these new diagnostic methods are more expensive that standard methods, they may still be worth the cost if we can prevent infections in patients. This study will help infection control practitioners to decide whether patients should be isolated with special precautions if they are MRSA carriers. The results of this study will contribute to better patient outcomes, lower hospital costs and more efficient use of resources.Read moreRead less
Molecular Mechanisms Of Low-level Vancomycin Resistance In Clinical Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$437,916.00
Summary
The common bacteria Staphylococcus aureus causes many infections in humans, and is becoming more resistant to antibiotic treatments, especially in hospitals. This project will determine how this bacteria is developing resistance to some of our last available antibiotics. This will provide an important basis for detecting and preventing this antibiotic resistance problem in future.
Inhibition Of Histidine Kinase Signal Sensing: A Novel Paradigm For Antimicrobial Development
Funder
National Health and Medical Research Council
Funding Amount
$464,144.00
Summary
Staphylococcus aureus (Golden staph) has been termed a superbug because of its remarkable ability to acquire resistance to virtually all antibiotics. Until recently, Golden Staph infections were almost always acquired in hospitals, but the increasing incidence of community-acquired S. aureus infections has rendered it a major public health threat in Australia. The aim of this research is to develop antimicrobial agents to combat antibiotic-resistant strains of Staphylococcus aureus.
Identification And Analysis Of Novel Replication Initiation Factors In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$311,789.00
Summary
Multi-drug resistant Golden staph is a serious medical problem around the world because strains are often resistant to commonly used treatments; new drugs are therefore urgently required. DNA replication is a fundamental process that is essential for the survival of all cellular organisms. This project aims to identify and characterise novel factors involved in DNA replication in Golden staph, which represent potential drug targets.
Efflux Mediated Multidrug Resistance In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$738,056.00
Summary
Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph), resistant to almost all available anti-staphylococcal agents, are responsible for serious infections among patients; in some hospitals such outbreaks reach epidemic proportions. In these bacteria, resistance has emerged to all classes of antimicrobial agents, including antibiotics and antiseptics-disinfectants commonly used in the hospital environment, largely due to the acquisition of resistance determinants. These determ ....Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph), resistant to almost all available anti-staphylococcal agents, are responsible for serious infections among patients; in some hospitals such outbreaks reach epidemic proportions. In these bacteria, resistance has emerged to all classes of antimicrobial agents, including antibiotics and antiseptics-disinfectants commonly used in the hospital environment, largely due to the acquisition of resistance determinants. These determinants encode proteins that provide the bacterial cell with a range of different biochemical mechanisms to evade antibiotic chemotherapy. Specifically, this project seeks to increase our understanding of proteins that confer resistance by pumping structurally-dissimilar antimicrobials out of the cell. The importance of these proteins in the biology of organisms is implied by the fact that an overwhelming majority of the drug targets are membrane proteins. Proteins which recognise such a broad spectrum of compounds are called multidrug resistance (MDR) proteins and present a disturbing clinical threat since the acquisition of one such system by a cell may simultaneously decrease its susceptibility to a number of antimicrobials. Similar MDR pumps are widespread in nature and are credited for resistance to antibiotics and other chemotherapeutic drugs in many pathogenic organisms and in human cancer cells. In this project, we aim to characterise the QacA MDR protein which is involved in pumping many different antimicrobial compounds from staphylococcal cells. We will identify the regions of the QacA MDR protein which bind the compounds and examine how the protein expels them to give resistance. These studies are a prerequisite for the design of more effective antibacterial compounds able to bypass these drug resistance pumps and will also provide fundamental knowledge applicable to the problem of MDR in other infectious diseases and cancer.Read moreRead less
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.