Circuit Breaker: Investigating The Regulatory Circuits Controlling Expression Of Drug Efflux Pumps In The Nosocomial Pathogen Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$515,244.00
Summary
Hospital-acquired infections caused by drug resistant pathogenic bacteria cost billions of dollars and increase patient pain and morbidity. This research will study the genes controlling multidrug efflux pumps in a major hospital-acquired bacterial pathogen, Acinetobacter baumannii. These efflux pumps make the bacteria resistant to antimicrobials by pumping them out of the cell. The results will allow us to better track drug resistant strains and will inform treatment options.
Antibiotic Tolerance And Small RNA Networks In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$521,559.00
Summary
Treatment of MRSA is restricted to last line antibiotics and treatment failure is associated with an intermediate tolerance to vancomycin. Regulatory molecules termed small RNA mediate responses to antibiotic challenge but their functions are poorly understood. This proposal will profile sRNA function to understand how they adapt S. aureus to antibiotic challenge. A molecular understanding of vancomycin-tolerance will inform development of diagnostics and treatment strategies.
Essential Gene Regulation In Multi-drug Resistant Golden Staph: A New Path Towards Control
Funder
National Health and Medical Research Council
Funding Amount
$784,452.00
Summary
New antibiotics effective against Golden Staph are urgently needed. This project will investigate a new approach to weaken Golden Staph defences with the potential to make existing antibiotics more effective at killing these bacteria.
Understanding The Role Of The Essential Regulator WalKR In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$555,239.00
Summary
Staphylococcus aureus is one of the most common human bacterial pathogens. This project aims to characterise an important global control system in S. aureus, and determine if chemical inhibitors of this control system could be used to treat S. aureus disease in the future.
Combating E. Coli Diarrhoea By Disarming Bacterial Virulence
Funder
National Health and Medical Research Council
Funding Amount
$674,737.00
Summary
E. coli causes severe and persistent diarrhoea which affects the health of millions of people worldwide. Although antibiotics may alleviate E. coli diarrhoea, these bacteria are becoming resistant to most drugs. In this study, we will use state-of-the-art technology to discover novel types of drug that treat and prevent infection with E. coli, without harming the beneficial bacteria in the gut.
Global Regulatory Networks That Control Virulence In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$531,557.00
Summary
This research focuses on the bacterium that is responsible for clostridial myonecrosis, or gas gangrene, an often fatal human infection. The objective is to determine how this bacterium controls the production of the various factors that are required to cause disease. The aims will be achieved by the integrated application of the latest techniques in microbiology and molecular biology and will result in a significant advancement in our knowledge of this complex regulatory process.
Regulation Of Virulence Gene Expression In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
This project involves the analysis of a bacterium that causes gas gangrene. We have shown that a previously unknown regulatory protein modulates the ability of this bacterium to cause disease. We aim to determine what turns on the protein's activity, how it controls the factors that contribute towards disease and what specific factors are involved in disease. The major outcome will be a better understanding of the mechanisms of virulence gene regulation, which will lead to improved methods of di ....This project involves the analysis of a bacterium that causes gas gangrene. We have shown that a previously unknown regulatory protein modulates the ability of this bacterium to cause disease. We aim to determine what turns on the protein's activity, how it controls the factors that contribute towards disease and what specific factors are involved in disease. The major outcome will be a better understanding of the mechanisms of virulence gene regulation, which will lead to improved methods of disease control.Read moreRead less
Molecular Analysis Of Regulation Of Virulence Gene Expression In Pathogenic E. Coli Strains (ETEC And Atypical EPEC)
Funder
National Health and Medical Research Council
Funding Amount
$289,258.00
Summary
Infectious diarrhoea is one of the commonest human afflictions worldwide, and is responsible for the deaths of millions of children each year. One of the principal causes of diarrhoea is pathogenic E. coli, which are classified into several groups according to the factors they employ to cause disease. One type of pathogenic E. coli, known as enterotoxigenic E. coli (ETEC), causes diarrhoea resembling cholera in children in less developed countries and in adult travellers to those countries. Anot ....Infectious diarrhoea is one of the commonest human afflictions worldwide, and is responsible for the deaths of millions of children each year. One of the principal causes of diarrhoea is pathogenic E. coli, which are classified into several groups according to the factors they employ to cause disease. One type of pathogenic E. coli, known as enterotoxigenic E. coli (ETEC), causes diarrhoea resembling cholera in children in less developed countries and in adult travellers to those countries. Another type is enteropathogenic E. coli (EPEC), which causes acute and persistent diarrhoea in children worldwide. Recent studies in Melbourne and Darwin have shown that EPEC are a particularly common cause of diarrhoea in children living in those cities. Individual groups of E. coli use different strategies to cause infection. In the case of ETEC, the key step in infection is the injection of bacterial toxins into intestinal cells. These toxins perturb the ability of these cells to transport water and electrolytes across their membrane. In contrast, infection with EPEC is characterised by intimate adherence of the bacteria to the lining of the intestine, causing structural damage to intestinal cells. Because the synthesis of virulence factors is an energy-costly process for bacteria, pathogenic varieties of E. coli have evolved sophisticated mechanisms to control the production of these factors, so that they are made only when needed, e.g., under environmental conditions like those in the gut. In this project, we will investigate the ways by which ETEC and EPEC sense and respond to environmental signals to produce their virulence determinants. The identification of specific control genes and proteins of these bacteria may lead to the development of novel diagnostic tools for EPEC and help us to devise new treatment strategies to block the production of virulence factors by pathogenic E. coli.Read moreRead less
Role In Disease Of A Novel Epigenetic Regulator Associated With The Hypervirulent Neisseria Meningitidis Clonal Complex 41/44
Funder
National Health and Medical Research Council
Funding Amount
$403,249.00
Summary
Neisseria meningitis is a major cause of meningococcal septicaemia and meningitis worldwide. We have identified a phase variable DNA methyltransferase present in disease isolates, some of which have caused meningococcal epidemics. This methyltransferase is involved in the regulation of proteins involved in infection and disease processes. We will investigate whether this regulation increases the ability of the bacteria to adapt to changing host environments and cause disease.