Harnessing The Type VI Secretion System ‘combat’ Arsenal Of A. Baumannii As A Source Of New Antimicrobials And Antimicrobial Targets
Funder
National Health and Medical Research Council
Funding Amount
$521,557.00
Summary
Infections caused by drug-resistant bacteria represent one of the greatest threats to human health. There is an urgent need to develop novel drugs and treatment strategies to combat infections by these drug-resistant organisms. We have shown that the bacteria A. baumannii uses a needle-like system to deliver lethal toxins into competitors. We will characterize these toxins so that we can manipulate them as weapons for controlling infections with multi-drug resistant bacteria.
Functional Genomic Analysis Of Multidrug Efflux In The Emerging Pathogen Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$550,226.00
Summary
Infections due to antimicrobial resistant organisms are a major public health issue. Acinetobacter baumannii is a bacterium that is increasingly being identified as a significant cause of serious antibiotic resistant infections, especially in the intensive care unit setting. Molecular studies in Acinetobacter to identify and characterise drug resistance proteins that pump antibiotics out of the cell will help understand the resistance capabilities and potential of this bacterium.
DNA sequencing allows us to see into the microbial world in fine detail. This enables us to investigate how bugs like bacteria cause infections and other diseases. In this fellowship, I will use DNA sequencing and analysis to investigate how bacterial infections are transmitted in hospitals and cities, how bacteria become resistant to the antibiotic drugs we use to treat infected people, and how the bacteria that live in our nose and throat contribute to development of asthma in young children.
Copper And Its Antibacterial Action: An Emerging Aspect Of Host Defence Against Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$454,858.00
Summary
This project will determine the way in which copper is used as an antimicrobial agent to kill Salmonella that reside inside the macrophage (white blood cell) of the host and also determine how Salmonella defends against copper-dependent killing. It will also determine the role of copper in the killing of extra-intestinal pathogens during sepsis. These results will provide information that can be used to manage and control infections intracellular and extracellular bacterial pathogens.
How Are Klebsiella Pneumoniae Infections Acquired In Hospital?
Funder
National Health and Medical Research Council
Funding Amount
$496,228.00
Summary
Klebsiella pneumoniae (Kp) bacteria are among the top causes of hospital infections and are often resistant to a wide range of antibiotics. While some hospital bugs are well-studied, we are considerably behind in our understanding of Kp, which can be carried in our bodies as a commensal without causing disease. Bacterial genomics will be used to dissect how Kp infections are acquired in hospital, including investigating the evidence for hospital transmission and the role of commensal carriage in ....Klebsiella pneumoniae (Kp) bacteria are among the top causes of hospital infections and are often resistant to a wide range of antibiotics. While some hospital bugs are well-studied, we are considerably behind in our understanding of Kp, which can be carried in our bodies as a commensal without causing disease. Bacterial genomics will be used to dissect how Kp infections are acquired in hospital, including investigating the evidence for hospital transmission and the role of commensal carriage in causing serious hospital infections.Read moreRead less
Novel Therapeutic And Preventive Strategies For Clostridium Difficile Infections.
Funder
National Health and Medical Research Council
Funding Amount
$508,556.00
Summary
The bacterium Clostridium difficile is the major cause of nosocomial diarrhoea in many countries, including Australia. More virulent isolates have recently emerged, leading to increased incidence and disease severity in many countries. This project will make a major contribution to our understanding of how these bacteria cause disease. Preventive or treatment measures based on these research findings will help to prevent or lessen the severity of any epidemics that occur in Australia.
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.
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