Expression And Secretion Of Large Clostridial Toxins From The Pathogenic Clostridia.
Funder
National Health and Medical Research Council
Funding Amount
$332,258.00
Summary
The large clostridial toxins are an important family of bacterial virulence factors that includes toxins from many disease-causing clostridial species. Despite their impact on public health, pathogenesis of disease caused by these bacteria is poorly understood. We will analyse how these bacteria regulate the production and secretion of the large toxins, which will give us a better understanding of the mechanisms of disease causation as well as identifying novel common therapeutic targets.
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.
A New Mechanism For Transposition Of Antibiotic Resistance Genes
Funder
National Health and Medical Research Council
Funding Amount
$501,839.00
Summary
Understanding how antibiotic resistance genes are acquired by bacteria is important if we are to understand how bacteria become resistant in so many antibiotics, limiting treatment options. This project will investigate the way a family of insertion sequences captures and then moves resistance genes. This mechanism contributes to resistance in many bacterial pathogens including ones that are resistant to many different antibiotics.
How Insertion Sequences Mobilize Antibiotic Resistance Genes
Funder
National Health and Medical Research Council
Funding Amount
$675,086.00
Summary
Resistance to all antibiotics available for treatment of bacterial infections is a cause for global concern (Word Health Organization, US Centres for Disease Control) as it also compromises therapies relying on antibiotics such as transplantation and cancer chemotherapy. This project will seek to understand how resistance genes are recruited and disseminated into different types of bacteria that repeatedly spread around the world.
Dissecting The Molecular Basis For Emerging Alcohol Tolerance In VRE
Funder
National Health and Medical Research Council
Funding Amount
$836,620.00
Summary
Infections caused by vancomycin resistant Enterococcus faecium (VREfm) are a major and growing problem in health care facilities around Australia. We have observed that VREfm is becoming significantly more resistant to killing by alcohol, probably due the increasing use of alcohol-based hand wash products. This project will identify how VREfm is becoming alcohol tolerant, knowledge that will be used to develop alternative disinfection methods or other intervention strategies to stop its spread.
Bacterial Pathogenomics: Whole-genome Sequencing To Investigate Infection Transmission, Pathogenesis And Antibiotic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$475,946.00
Summary
As bacterial superbugs – resistant to multiple antibiotics – dominate the headlines, the pipeline for new antibiotics has all but dried up. High-throughput DNA sequencing heralds a golden opportunity for infectious disease research. By studying the entire collection of genes - the genome - of large numbers of multidrug resistant bacterial strains, we aim to better understand the genetic changes that govern the emergence and global spread of superbugs and translate these findings into the clinic.
Origins And Relationships Of Shigella And Enteroinvasive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$377,310.00
Summary
Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoe ....Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoea in less developed countries and has also caused large outbreaks in developed countries. It is now clear that Shigella and E. coli are really one species. EIEC and Shigella strains are variants of E. coli with humans as the only host. However separation of the two in all records and most studies means that there is no integrated understanding of the forms. We aim to study the relationships of Shigella and EIEC and expect significant insights into the origins of Shigella-EIEC. This will facilitate diagnosis and understanding of the disease(s) and lead to a far better classification . EIEC-Shigella strains have arisen from other E. coli independently. This has happened seven times in the derivation of Shigella and we expect more such events with EIEC. An interesting phenomenon during this process is that strains tend to lose metabolic functions. In this study we will look at what, why and how functions are lost. O antigens are important in evading the host immune system. Shigella strains obtained many O antigens, the majority apparently from other species. This is quite likely the key to its success. We will look at how Shigella obtained new O antigens. This project will be significant in the understanding of Shigell-EIEC, a very significant human pathogen, and in general for understanding emergence of new pathogens.Read moreRead less
Identifying The Physiological Conditions That Promote Lateral Gene Transfer And Evolution Of New Streptococcal Pathovars
Funder
National Health and Medical Research Council
Funding Amount
$415,907.00
Summary
In the last few decades, the diseases caused by the three human pathogens, groups A, B and G streptococcus have undergone a transformation. The exchange of DNA between these species is speculated to play a role in this changing disease association. In this proposal we will identify the specific physiological and growth conditions that promote DNA transfer. Such information may help in our understanding of how new pathogenic strains of streptococci arise.
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
Interrogation Of Streptococcal Genomic Epidemiology Within Disease Endemic Regions
Funder
National Health and Medical Research Council
Funding Amount
$325,896.00
Summary
Group A streptococcal (GAS) bacterial infections within the Indigenous populations of Northern Australia are amongst the highest in the world. This project uses comparative bacterial genomics to examine current and historical outbreaks of GAS disease in Northern Australia relative to globally sourced GAS. This will be used to examine the spread of disease causing GAS between remote communities as well as investigating genetic markers of disease and informing therapeutic interventions.