Molecular Mechanisms Of Low-level Vancomycin Resistance In Clinical Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$437,916.00
Summary
The common bacteria Staphylococcus aureus causes many infections in humans, and is becoming more resistant to antibiotic treatments, especially in hospitals. This project will determine how this bacteria is developing resistance to some of our last available antibiotics. This will provide an important basis for detecting and preventing this antibiotic resistance problem in future.
Once treatable infections are becoming deadly because bacteria are developing broad antibiotic resistance. New medicines are urgently needed. Microbes themselves are the richest known source of new antibiotics but finding the 'good bugs' is like finding a needle in a microbial haystack. This project will use state-of-the art science to screen a previously overlooked source of rich microbial biodiversity and find new antibiotics.
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.
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.
Pacing Across The Membrane: Characterising The PACE Family Of Multidrug Efflux Systems
Funder
National Health and Medical Research Council
Funding Amount
$640,815.00
Summary
The World Health Organisation recognises bacterial antimicrobial resistance as one of the major threats to human health worldwide. Multidrug efflux pumps are an important class of resistance proteins that sit in the bacterial cell membrane and move antimicrobials out of the cell. We recently discovered the first new family of multidrug efflux pumps to be described in 15 years. Our project will define the precise resistance functions of this family and identify ways to block their function.
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
Understanding The Disease Burden And Antibiotic Resistance In Patients With Bloodstream Infections Caused By Enterobacteriaceae In Australia
Funder
National Health and Medical Research Council
Funding Amount
$135,285.00
Summary
This study aims to establish the epidemiology of bloodstream infections caused by Enterobacteriaceae (enteric or gut bacteria) in Australia, by examining infection rates, types of antibiotic resistance present, and which treatments optimise clinical outcomes.
This project uses latest genomic technologies to advance our understanding of how bacteria cause disease and finding new antibiotics/approaches to stop the spread of multi-drug resistant hospital superbugs.
Interactions Between Integrative Genomic Islands And Plasmids; Role In The Spread And Loss Of Antibiotic Resistance And Pathogenicity Determinants
Funder
National Health and Medical Research Council
Funding Amount
$776,465.00
Summary
Mobile elements that integrate into bacterial chromosomes at a specific site contribute pathogenicity and antibiotic resistance determinants to their bacterial host but only a few are able to move themselves into new hosts. Some plasmids and some elements can help certain others. In this project, genetic approaches will be used to investigate how plasmids and integrative elements help one another move into a new bacterium or compete with one another to stay in the same cell.
Interactions Between Host And The Gut Microbiome In The Pathogenesis Of Ankylosing Spondylitis And Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$572,227.00
Summary
Ankylosing spondylitis (AS) and Crohn's disease (CD) are common immune-mediated diseases affecting primarily the joints of the spine and the gut respectively. Genes play a major role in determining the risk of each disease, and it is likely that those genes cause the disease by interaction with some environmental factor, most likely bacteria residing in the gut. This study aims to test that hypothesis by profiling the bacteria in the gut of patients with the diseases and healthy subjects.