Crohn’s disease (CD), an inflammatory disorder of the gut, is thought to result from an inappropriate response to an environmental trigger, likely gut bacteria. This project will assess differences in microbial communities and host gene expression of early- and late-stage CD tissues. A greater understanding of the differences in mucosal gene expression induced by specific bacteria may provide insights into the pathophysiology of CD, and could conceivably guide therapeutic choices in the future.
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
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.
Linking Genomics Of Burkholderia Pseudomallei To Melioidosis: Diversity Of Clinical Manifestations, Changing Epidemiology And Microevolution In Chronic Carriage.
Funder
National Health and Medical Research Council
Funding Amount
$602,769.00
Summary
The Darwin Prospective Melioidosis Study has documented 761 cases since 1989, with 102 fatalities. This study has led to improved therapy and public health initiatives. New technology to sequence whole bacterial genomes provides an opportunity to determine why urban melioidosis is increasing and to analyse this unique 22+ year set of bacteria and their linked patient data to find the important bacterial virulence factors, forming a foundation for future diagnostics, therapeutics, and vaccines.
The pneumococcus is a major cause of bacterial pneumonia, sepsis and meningitis especially in children and the elderly. Antibiotic-resistant pneumococci are becoming more prevalent, and available vaccines have major shortcomings. We propose to identify and characterise the factors produced by this organism during infection that enable it to cause invasive disease. Such factors could be incorporated into protein-based pneumococcal vaccines currently under development.
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.
Genome Wide Investigations Of Mycobacterium Tuberculosis To Reveal Processes Of Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$396,341.00
Summary
Tuberculosis remains a global health burden of staggering proportions. Around 1 in 3 people are infected with Mycobacteria tuberculosis, the organism responsible for the disease, which kills 2 million people annually. The emergence of strains now resistant to almost all of our front line drugs has placed extra pressure on researchers who are attempting to develop new protective vaccines and the critical antibiotics required to eradicate the disease. Furthermore the current global HIV pandemic is ....Tuberculosis remains a global health burden of staggering proportions. Around 1 in 3 people are infected with Mycobacteria tuberculosis, the organism responsible for the disease, which kills 2 million people annually. The emergence of strains now resistant to almost all of our front line drugs has placed extra pressure on researchers who are attempting to develop new protective vaccines and the critical antibiotics required to eradicate the disease. Furthermore the current global HIV pandemic is making the situation far worse as HIV kills the very cells of the body that protect us from tuberculosis. This research project will fill the significant gaps in our knowledge of M. tuberculosis infection, specifically identify the genes of the organism which allow it to invade and spread throughout the body. M. tuberculosis infection consists of 3 characteristic stages, i.e. colonisation, spread and long term survival in specialised structures called granulomas. It is from these granulomas that the bacterium can emerge after long periods of inactivity to cause clinical tuberculosis. Using a mouse model of infection I will define the genes needed by the bacterium to survive at these 3 key stages of disease thereby providing for a better knowledge base from which to design new vaccine strategies and to create effective drugs.Read moreRead less
Non-coding RNA Regulation Of Virulence In Enterohaemorrhagic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$389,313.00
Summary
Shiga toxins cause potentially fatal haemolytic uremic syndrome (HUS) and are transferred between bacterial pathogens by bacteriophage (bacterial viruses). We have recently found that the Shiga toxin encoding bacteriophage encodes an unusually large number of non-coding RNAs (RNA regulators of gene expression). This Project aims to understand how these RNA regulators benefit the Shiga toxin bacteriophage and use this knowledge to develop interventions that will prevent expression of the toxin.
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.