Dissecting The Molecular Basis For Emerging Alcohol Tolerance In VRE
Funder
National Health and Medical Research Council
Funding Amount
$836,620.00
Summary
Infections caused by vancomycin resistant Enterococcus faecium (VREfm) are a major and growing problem in health care facilities around Australia. We have observed that VREfm is becoming significantly more resistant to killing by alcohol, probably due the increasing use of alcohol-based hand wash products. This project will identify how VREfm is becoming alcohol tolerant, knowledge that will be used to develop alternative disinfection methods or other intervention strategies to stop its spread.
Anti-sporulation Strategies For Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$651,559.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These strains have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains spread and will provide knowledge that is critical for developing improved strategies for preventing these infections.
Long-term Macrolide Therapy; Oropharyngeal Dysbiosis And The Spread Of Resistant Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$384,153.00
Summary
Use of macrolide therapy for chronic lung diseases is increasing rapidly. We will determine the impact of long-term macrolide antibiotic use on upper airway bacteria in patients with lung disease, and assess its contribution to antibiotic resistance in the wider community. We will investigate the mechanism by which this therapy achieves benefit and assess interference with bacterial signalling as a means to improve treatment efficacy and reduce induction of antibiotic resistance.
Curing Antibiotic Resistance: Probiotic Plasmids And Microbial Husbandry In The Enterobacteriaceae
Funder
National Health and Medical Research Council
Funding Amount
$560,832.00
Summary
The most troublesome emerging antibiotic resistance is coming in the form of addictive and promiscuous 'pest' plasmids, carrying dangerous genes that defeat antibiotics used for the most severe infections. We currently manage this problem by isolating infected patients and trying to design new antibiotics. Our approach eradicates these plasmids and renders the host bacterium antibiotic susceptible again, thereby restoring the natural ecology in animals and potentially in humans.
Legionella bacteria are the major cause of Legionnaire’s Disease, a common form of acute pneumonia. Here we will study how the bacteria avoid killing in human cells by establishing an intracellular niche that is sequestered from the normal host cell defence pathways. In particular we hope to understand how the bacteria regulate a major protein modification pathway called ubiquitination.
Tuberculosis is one of the most threatening infectious diseases worldwide due to the low efficiency of the only licensed anti-tuberculosis vaccine, BCG. This project aims to interrogate two previously neglected immune mechanisms and their potential to enhance vaccine-induced immunity by incorporating these mechanisms into new genetically modified BCG strains. We will also investigate alternative BCG vaccination routes to generate long-lived immune cells that can rapidly control the infection.
Identification Of Proteins Specific To Transmissible Pseudomonas Aeruginosa In Cystic Fibrosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$443,007.00
Summary
Cystic fibrosis (CF) is the most common autosomal recessive disorder in humans, affecting 1:2000 people. Mortality is often caused by Pseudomonas aeruginosa lung infections which have recently been shown to occur not only environmentally but also via person-person contact, usually during CF clinic visits. This project will elucidate the molecular traits responsible for these 'epidemic' P. aeruginosa infections, with the aim of finding novel therapeutics and infection control strategies.
Killing Infected Cells As A Mechanism To Eradicate Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$1,085,770.00
Summary
Mycobacterium tuberculosis (Mtb), the causative agent of TB, is rapidly becoming resistant to all antibiotics and this disease kills more than one million people each year. This underscores the urgent need to develop new treatments for this disease. We are developing a therapy that kills Mtb infected cells and may help to eradicate infection. This highly novel approach to the treatment of TB would have profound implications for the 2 billion people infected with this pathogen.
Role Of Macrophages In Uropathogenic E. Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Urinary tract infections (UTI) are one of the most common types of infections in humans. They are also a major cause of septic shock, a condition with high fatality rates. Uropathogenic Escherichia coli (UPEC) are the major microbes causing UTI in humans. This project addresses the role of an immune cell type, the macrophage, in UPEC-mediated disease. The outcomes of this project will be a better understanding of how UPEC causes disease, and potentially new treatment regimes for UTI.
Enhancing Host Defence Mechanisms In Severe Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$830,447.00
Summary
New options to treat bacterial infections are needed because of the rapid increase in antibiotic resistance. One very attractive strategy is to boost the body’s own defence mechanisms against bacteria. This project defines novel molecular mechanisms that can be manipulated to better control a bacterial infection. Novel drugs targeting these molecular pathways are already being developed, albeit for cancer. This project will help assess if these drugs may be useful to treat infections.