Evolution And Pathogenicity Of NDM-1 Positive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$643,275.00
Summary
Antibiotic resistance (AR), as highlighted by the WHO, is the most pressing medical need of the 21C – some infections are now untreatable. Our research will focus on the new "superbug" NDM-1 positive E. coli. We will correlate AR and pathogenicity and explore the evolution of these "superbugs" using state-of-the-art sequencing. This research will benefit Australian medicine by predicting timelines of AR epidemics and by conducting the first analyses on the virulence potential of these strains.
Non-coding RNA Regulation Of Virulence In Enterohaemorrhagic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$389,313.00
Summary
Shiga toxins cause potentially fatal haemolytic uremic syndrome (HUS) and are transferred between bacterial pathogens by bacteriophage (bacterial viruses). We have recently found that the Shiga toxin encoding bacteriophage encodes an unusually large number of non-coding RNAs (RNA regulators of gene expression). This Project aims to understand how these RNA regulators benefit the Shiga toxin bacteriophage and use this knowledge to develop interventions that will prevent expression of the toxin.
Regulatory Networks Controlling The Interaction Of Neisseria Gonorrhoeae With The Human Host
Funder
National Health and Medical Research Council
Funding Amount
$361,091.00
Summary
What does Neisseria gonorrhoeae switch on when entering a human cell? Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease (STD) gonorrhoea and globally causes approximately 20-60 million new cases per annum (WHO). Gonococcal infection is the leading cause of pelvic inflammatory disease in women and ~ one third of patients will become infertile. Increased levels of resistance to traditional antibiotics have raised concerns for future treatment options. To date no succ ....What does Neisseria gonorrhoeae switch on when entering a human cell? Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease (STD) gonorrhoea and globally causes approximately 20-60 million new cases per annum (WHO). Gonococcal infection is the leading cause of pelvic inflammatory disease in women and ~ one third of patients will become infertile. Increased levels of resistance to traditional antibiotics have raised concerns for future treatment options. To date no successful vaccine strategies have been developed for this organism, primarily because the cell surface proteins elicit limited immunological protection against other strains. To enable the development of innovative approaches to the control of gonococcal infections, we propose to investigate the regulatory networks in gonococci that are important for initial colonization and survival in the human host. We will examine the role of a class of proteins, called sigma factors, that control the expression of a large number of genes in a concerted fashion. The sigma factors themselves do not recognize environmental signals, but their activity is controlled by a complicated array of proteins that are responsive to changing conditions in the bacterial cell. We have for the first time in any bacterial pathogen, identified all of the genes controlled by sigma factors in the obligate human pathogen, Neisseria gonorrhoeae. We have also found that the mechanisms controlling the activity of the sigma factors in this organism are different to those found in other bacterial pathogens. Our aim is to understand the mechanisms that control sigma factors and to gain insight into how N. gonorrhoeae sense and responds to the host cell during infections.Read moreRead less
Mechanisms Of Stable Gene Inheritance In Multiresistant Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$620,357.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections in Australia and around the world. The bacteria have mechanisms that cause efficient inheritance of resistance genes, even when antibiotics are no longer being used. This project will elucidate key aspects of such mechanisms so that treatments can be devised that interfere with the development and maintenance of resistance.
Horizontal And Vertical Transmission Mechanisms Of Staphylococcus Aureus Multiresistance Plasmids
Funder
National Health and Medical Research Council
Funding Amount
$408,993.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections. The bacteria have mechanisms that cause efficient transmission of resistance genes to their offspring as well as to other strains. This project aims to elucidate key features of these mechanisms so that treatments can be devised that disrupt the maintenance and transfer of resistance, so as to prolong the effectiveness of antibiotics.
Redefining Antibiotic Resistance Plasmid Transfer In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$735,585.00
Summary
Multidrug-resistant Golden Staph bacteria are a major health problem. Resistance develops rapidly because bacteria efficiently acquire/share resistance genes. Our discoveries suggest DNA transfer mechanisms are far more diverse and widespread than previously expected and this has wide-reaching implications for numerous pathogenic organisms. This project aims to define the prevalence and key features of each mechanism so treatments can be devised to disrupt the evolution and spread of resistance.
Expression And Secretion Of Large Clostridial Toxins From The Pathogenic Clostridia.
Funder
National Health and Medical Research Council
Funding Amount
$332,258.00
Summary
The large clostridial toxins are an important family of bacterial virulence factors that includes toxins from many disease-causing clostridial species. Despite their impact on public health, pathogenesis of disease caused by these bacteria is poorly understood. We will analyse how these bacteria regulate the production and secretion of the large toxins, which will give us a better understanding of the mechanisms of disease causation as well as identifying novel common therapeutic targets.
Rapid Prediction Of Antibiotic Resistance In The Enterobacteriaceae: Making Use Of Restricted Diversity In Mobile Resistance Gene Pools
Funder
National Health and Medical Research Council
Funding Amount
$385,032.00
Summary
Immediate treatment of patients suffering life-threatening bacterial infections with effective antibiotics greatly improves their chances of survival, but antibiotic resistance increasingly complicates this treatment. Currently such resistance cannot be detected in time to help decide the best antibiotic to use. We aim to define a small set of the many known antibiotic resistance genes that can be used accurately predict resistance in rapid tests using modern detection systems.