Real-Time Molecular Typing Systems In Infection Control: Design And Effectiveness
Funder
National Health and Medical Research Council
Funding Amount
$82,554.00
Summary
MRSA is a major cause of hospital-acquired infection. Molecular typing identifies how a patient managed to contract MRSA in the hospital, and if the strain they have is particularly dangerous. This study will develop a rapid typing protocol then implement it routinely, to determine whether providing this information to infection control staff in a more timely fashion will lead to reduced MRSA infections in hospitals.
QacA-mediated Multidrug Resistance And Export In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$497,250.00
Summary
Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph) which are resistant to almost all available anti-staphylococcal agents are responsible for serious infections among hospitalised 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 deter ....Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph) which are resistant to almost all available anti-staphylococcal agents are responsible for serious infections among hospitalised 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 for proteins which 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 which confer resistance by pumping a variety of structurally-dissimilar antimicrobials out of the bacterial cell. Proteins which recognise such a broad spectrum of compounds are called multidrug resistance 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 multidrug pumps are widespread in nature and are credited for resistance to antibiotics and other chemotherapeutic drugs in many pathogenic organisms, such as the bacteria responsible for tuberculosis, and in human cancer cells. In this project, we aim to characterise the QacA multidrug resistance protein which is involved in pumping many different antimicrobial compounds from staphylococcal cells. We will identify the regions of the QacA multidrug resistance 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 or block these drug resistance pumps, and will also provide fundamental knowledge applicable to the problem of multidrug resistance in other infectious diseases and cancer.Read moreRead less
Molecular And Genetic Basis Of Colistin Resistance In Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Acinetobacter baumannii is a bacterium that causes hospital acquired infections which have become difficult to treat due to the bacteria developing resistance to most antibiotics in routine use. Colistin is now widely used as 'salvage' therapy in patients with these infections. Colistin resistance is currently low but is an emerging problem. As a first step in combating this problem this project will identify how this bacterium becomes resistant to colistin.
QacA-mediated Multidrug Resistance And Export In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph) which are resistant to almost all available anti-staphylococcal agents are responsible for serious infections among hospitalised 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 deter ....Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph) which are resistant to almost all available anti-staphylococcal agents are responsible for serious infections among hospitalised 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 for proteins which 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 which confer resistance by pumping a variety of structurally-dissimilar antimicrobials out of the bacterial cell. Proteins which recognise such a broad spectrum of compounds are called multidrug resistance 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 multidrug pumps are widespread in nature and are credited for resistance to antibiotics and other chemotherapeutic drugs in many pathogenic organisms, such as the bacteria responsible for tuberculosis, and in human cancer cells. In this project, we aim to characterise the QacA multidrug resistance protein which is involved in pumping many different antimicrobial compounds from staphylococcal cells. We will identify the regions of the QacA multidrug resistance 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 multidrug resistance in other infectious diseases and cancer.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
Multidrug Resistance Regulatory Protein QacR From Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$459,750.00
Summary
One of the most significant mechanisms of drug resistance is the export of antibiotics and other chemotherapeutic drugs from the cell. Drug export systems are an important medical problem due to their frequent occurrence in bacteria and parasites which cause human disease, and in human cancer cells. Proteins which recognise and export a broad range of drugs from a cell are called multidrug efflux pumps. These multidrug efflux systems present a serious threat to patient care and to successful the ....One of the most significant mechanisms of drug resistance is the export of antibiotics and other chemotherapeutic drugs from the cell. Drug export systems are an important medical problem due to their frequent occurrence in bacteria and parasites which cause human disease, and in human cancer cells. Proteins which recognise and export a broad range of drugs from a cell are called multidrug efflux pumps. These multidrug efflux systems present a serious threat to patient care and to successful therapy, since the ability to produce a single protein simultaneously renders the cell or organism resistant to several different drugs. Strains of the bacterial pathogen Staphylococcus aureus or Golden Staph, which are endemic in hospitals world-wide, contain an example of such a multidrug exporter, the QacA multidrug efflux pump. QacA exports at least 30 different antimicrobial compounds, including antiseptics and disinfectants. Production of this protein is regulated by a sensor protein, QacR, which detects the presence of a number of these antimicrobial compounds. To understand how the QacR sensor protein can recognise such a wide variety of compounds, we will identify and structurally characterise the regions of the QacR multidrug regulatory protein which bind these compounds. Additionally, we will examine the means by which QacR regulates the production of the QacA pump protein. This project will provide fundamental knowledge that will not only help with understanding the important process of multidrug resistance but will also enable the rational design of more effective antibacterial compounds that either block or evade these multidrug efflux systems.Read moreRead less
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
Multidrug Resistance Regulatory Protein QacR From Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
One of the most significant mechanisms of drug resistance is the export of antibiotics and other chemotherapeutic drugs from the cell. Drug export systems are an important medical problem due to their frequent occurrence in bacteria and parasites which cause human disease and in human cancer cells. Proteins which recognise and export a broad range of drugs from a cell are called multidrug efflux pumps. These multidrug efflux systems present a serious threat to patient care and to successful ther ....One of the most significant mechanisms of drug resistance is the export of antibiotics and other chemotherapeutic drugs from the cell. Drug export systems are an important medical problem due to their frequent occurrence in bacteria and parasites which cause human disease and in human cancer cells. Proteins which recognise and export a broad range of drugs from a cell are called multidrug efflux pumps. These multidrug efflux systems present a serious threat to patient care and to successful therapy, since the ability to produce a single protein simultaneously renders the cell or organism resistant to several different drugs. Strains of the bacterial pathogen Staphylococcus aureus or Golden Staph, which are endemic in hospitals world-wide, contain an example of such a multidrug exporter, the QacA multidrug efflux pump, which exports at least 30 different antimicrobial compounds, including antiseptics and disinfectants. Production of this protein is regulated by a sensor protein, QacR, which detects the presence of a number of these antimicrobial compounds. To understand how the QacR sensor protein can recognise such a wide variety of compounds, we will identify and structurally characterise the regions of the QacR multidrug regulatory protein which bind these compounds. Additionally, we will examine the means by which QacR regulates the production of the QacA pump protein. This project will provide fundamental knowledge that will not only help with understanding the important process of multidrug resistance but will also enable the rational design of more effective antibacterial compounds that either block or evade these multidrug efflux systems.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
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.