Exploitation Of Bacterial Transcription Initiation As A Target For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Antibiotic resistant infections from 'superbugs' are a major health problem. We will exploit information we have gathered on the machinery that copies genetic information into a message to discover chemical compounds that can be used for the development of new antibiotics with a novel mechanism of action.
Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
Genes Of Mycobacterium Tuberculosis Essential For Latent Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
One third of the worlds population is latently infected with M. tuberculosis, the bacteria which causes TB. We have identified key genes in M. tuberculosis that enable the bacterium to shut-down and become latent. This project will investigate these genes, identify their role and yield vital information for a new paradigm of drug and vaccine development. Improved vaccines and drugs which can target and inhibit latency would be of enormous benefit to the global community.
A New Class Of Inhibitors For The Treatment Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$720,691.00
Summary
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, with 1.3 million deaths annually. Some strains of the TB bacterium are resistant to all available drugs. We have identified novel chemical structures that display potent and specific activity against pathogenic mycobacteria. In this proposal we will develop optimised derivatives with more potent activity against mycobacteria, assess their stability and toxicity and determine their mode of action.
Understanding The Role Of O-linked Glycosylation In Burkholderia Cenocepica For Host Survival Using Proteomic Approaches
Funder
National Health and Medical Research Council
Funding Amount
$222,004.00
Summary
The bacteria Burkholderia cenocepecia (Bc) is a common infection of Cystic Fibrosis suffers in Australia. ~20% CF patients infected with Bc will die due to lung failure. Due to this high death rate there is an urgent need to understand how Bc survives and causes disease in the host. This grant aims to understand how the attachment of sugars, a process known as glycosylation, affects the ability of Bc to survive in mammalian cells.
Host-pathogen Interactions In Clostridial Myonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$897,617.00
Summary
This project will show how the bacteria that cause gas gangrene interact with host cells in an infection. We will examine the expression of genes from both the host and the pathogen in a mouse disease model. The aims are to determine the impact of bacterial genes that are differentially regulated in an infected lesion, how gene expression of both the host and pathogen is modulated throughout the course of an infection and the role of host pathways in controlling the infection process.
The Glyco-interactome Of Pathogenic Neisseria: Understanding Disease And Defining Vaccine Targets
Funder
National Health and Medical Research Council
Funding Amount
$431,012.00
Summary
In order to infect humans and cause disease, many bacteria rely on interactions with carbohydrate (sugar) structures on human cells. This project aims to characterise the sugar interactions that enable Neisseria meningitidis (causes meningitis, sepsis) and Neisseria gonorrhoeae (causes gonorrhoea, associated with infertility and increased transmission of HIV) to cause disease. This will increase our understanding of host-pathogen interactions and aid development of new vaccines and therapeutics.
An Ace Up Their Sleeve: Characterisation Of A Novel Family Of Drug Efflux Systems Represented By The Acinetobacter AceI Exporter
Funder
National Health and Medical Research Council
Funding Amount
$400,286.00
Summary
Chlorhexidine is widely used as an antiseptic in products such as skin washes, soaps, mouthwashes, disinfectants and preservatives. We have recently discovered a novel bacterial protein which pumps chlorhexidine out of bacterial cells to make them resistant to this antiseptic agent. This proposal aims to understand this resistance mechanism and to find inhibitors which could be applied in clinical settings to augment the activity of chlorhexidine.
Reversing Antibiotic Resistance With Efflux Pump Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$494,174.00
Summary
Antibiotic resistance in dangerous pathogens is one of the greatest threats to human health of the 21st century. The main cause of multidrug resistance is the presence of drug efflux pumps, which remove antibiotics from the bacterial cell thereby lowering the antibiotic concentration inside the cells to sub-toxic levels. We will use our expertise on these efflux pumps and on how to inhibit them to develop compounds that could reverse resistance and restore the activity of antibiotics.