Regulation From The Outside: Control Of Transport And Assembly Of Major Cell Wall Components In Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$652,019.00
Summary
Tuberculosis (TB) kills nearly two million people each year while the causative bacterial species, Mycobacterium tuberculosis, infects one-third of the entire human population. An alarmingly high rate of TB exists in Australia's indigenous population. This proposal aims to identify and characterise essential processes that regulate synthesis of the outer coat of the bacterium, which are potential targets for new drugs for the treatment of this devastating disease.
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.
Molecular Basis For Conjugative Transfer Of Antibiotic Resistance Genes In Gram Positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$872,660.00
Summary
There has been growing concern about the increasing level of antibiotic resistance in bacterial pathogens. We will use a model genetic element to determine the mechanism by which an important class of pathogenic bacteria can acquire new resistance genes by a process known as horizontal gene transfer. The project will significantly enhance our understanding of how major hospital and community acquired pathogenic bacteria can rapidly evolve to become resistant to different antimicrobial agents.
The Mechanism Of Conjugative Transfer Of Antibiotic Resistance Genes In Gram Positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
Antibiotic resistant bacteria pose a serious threat to the health of Australians. We will determine how antibiotic resistance genes spread from one bacterium to another. Using a disease-causing bacterium as model we will determine the mechanism by which this gene transfer process occurs and the structure and function of the key components. The result will be major advances in our understanding of the evolution of the antibiotic resistant bacteria that are major causes of human disease.
Investigating The Mechanisms Of Regulation Of Mycobacterial Cell Wall Biosynthesis
Funder
National Health and Medical Research Council
Funding Amount
$597,349.00
Summary
Tuberculosis (TB) kills around two million people each year while the causative bacterial species, Mycobacterium tuberculosis, infects one-third of the entire human population. An alarmingly high rate of TB exists in Australia's indigenous population. This proposal aims to identify and characterise essential processes involved in synthesis of the outer coat of the bacterium which are potential targets for new drugs for the treatment of this devastating disease.
Role Of IS26 In Antibiotic Resistance Gene Recruitment, Dissemination And Expression
Funder
National Health and Medical Research Council
Funding Amount
$457,879.00
Summary
Antibiotic resistance is increasing, compromising the efficacy of front-line antibiotics. Untreatable infections due to bacteria that are resistant to all available antibiotics are being seen more often. To control the spread of resistance, an understanding of how resistance arises and is spread among bacteria is needed. This requires information about how the genetic elements that mobilize them work. This project will study one of the most important of these elements.
Molecular Mechanisms Of Persistence Of Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$398,142.00
Summary
Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacte ....Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacteria. M. tuberculosis is able to survive and adapt to those harsh environments. M. tuberculosis has an especially thick and tough cell wall which protects it. M. tuberculosis can adapt to the environments it encounters in a patient by changing their cell walls. The wall also protects mycobacteria from chemicals so it is resistant to many common antibiotics. There are some drugs to treat TB however M. tuberculosis is building up resistance to those drugs so we need to find new ones We will determine how mycobacteria synthesize their special cell wall and how they adapt during an infection. If we know how the details of how M. tuberculosis protects itself then we can find potential weakness which could be targets for the development of new drugs to treat TB.Read moreRead less
A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a ....A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a population some cells will lack genes that others have. Some of these shared genes apart from antibiotic resistance can be a concern and include traits that make some bacteria pathogenic. Thus, two cells of the same species may have very different abilities to cause disease based on what additional genes they carry. Genomics is becoming one of the great scientific revolutions of the 21st century. Over 160 microbial genomes have been sequenced to date and from these studies we have also learned many important things including how some bacteria cause disease. Mobile DNA presents unique challenges to microbial genomics however since different individuals in a species can have many different genes. Thus genomics on even many individuals of a species may miss bacterial genes important to us. Here we will be applying genomics in a way that specifically targets those genes that are shared. This will have many benefits. We will be able to greatly increase our rate of discovery of medically important and other genes in way that is targeted. This approach will allow us to discover these shared genes in a way that is much more cost effective and faster than conventional whole cell genomics. It will also allow us to gain an understanding of how benign bacteria associated with humans may act as reservoirs for passing on harmful genes to bacteria that cause hospital infections.Read moreRead less
Identifying Key Players In The Spread Of Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$817,448.00
Summary
Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australi ....Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australia.Read moreRead less