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The Glyco-interactome Of Pathogenic Neisseria: Understanding Disease And Defining Vaccine Targets
Funder
National Health and Medical Research Council
Funding Amount
$431,012.00
Summary
In order to infect humans and cause disease, many bacteria rely on interactions with carbohydrate (sugar) structures on human cells. This project aims to characterise the sugar interactions that enable Neisseria meningitidis (causes meningitis, sepsis) and Neisseria gonorrhoeae (causes gonorrhoea, associated with infertility and increased transmission of HIV) to cause disease. This will increase our understanding of host-pathogen interactions and aid development of new vaccines and therapeutics.
Role In Disease And Vaccine Potential Of Cell Surface O-linked Glycoproteins In Pathogenic Neisseria.
Funder
National Health and Medical Research Council
Funding Amount
$212,347.00
Summary
Bacteria that have adapted to life exclusively in the human host have developed unique strategies to colonize the host and to evade the immune response. An emerging strategy is modification of bacterial surface proteins with sugars or other modifications. Our data suggests a key role for these modifications in disease. We will investigate how the modifications are made, discover structures of novel modifications and determine their precise role in disease.
Gonococcal Vaccine Development Guided By A Cross-protective Meningococcal Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$826,490.00
Summary
Neisseria gonorrhoeae, the bacteria responsible for the sexually transmitted infection gonorrhoea, is a significant health problem worldwide. Control of gonorrhoea depends on the development of a vaccine due to the continuing increase of antibiotic resistance and the staggering outcomes of infection, including infertility and increased transmission of HIV. This work will identify vaccine targets and determine the way in which they mediate protection against gonococcal infection.
Design And Implementation Of A Human Challenge Model For Neisseria Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Gonorrhoea is a major public health problem that can lead to severe disease and promote the spread of HIV. Gonorrhoea infections are increasing worldwide and the spread of antibiotic resistant gonorrhoea is a critical health threat. This study aims to develop a controlled infection model for male throat and genital gonorrhoea infection in order to improve scientific understanding of gonorrhoea infection and responses to novel antibiotic treatment; and provide insights into vaccine development.
A group of bacteria called Neisseria cause human-specific infections. To initiate infection, the bacteria must produce a hair-like surface structure, the pilus. The pilus consists mainly of a protein called pilin, and we now understand how pilin production is controlled. However 20 other genes are also involved in pilus production. This project aims to understand how these other genes are controlled and coordinated to assemble this structure that is central to the ability to cause disease.
Glycosylation Of Pili In Pathogenic Neisseria: Function In Disease And Potential As A Vaccine Antigen
Funder
National Health and Medical Research Council
Funding Amount
$150,880.00
Summary
Disease caused by Group B Neisseria meningitidis and Neisseria gonorrhoeae remain a significant health problem worldwide. There are currently no vaccines available for either of these bacteria. A surface structure found on these bacteria, called pili, are key in host colonisation and disease. Genetics and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. The role of glycosylation in the disease process is not ....Disease caused by Group B Neisseria meningitidis and Neisseria gonorrhoeae remain a significant health problem worldwide. There are currently no vaccines available for either of these bacteria. A surface structure found on these bacteria, called pili, are key in host colonisation and disease. Genetics and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. The role of glycosylation in the disease process is not known. It is possible that the glycosylation of pili is required for attachment to host cells or perhaps in evasion of the immune system. In our current studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria which make structre that are know. We have also identified a series of new genes we believe are also involved in glycosylation. Some of these genes are involved in the biosynthesis of unknown structures and are common in bacteria isolated from patients with meningitis. We will identify these stuctures and characterise bacteria in which these genes have been inactivated so that we can examine the role of pili glycosylation in colonisation and disease. This study has the potential to yield important new information about the process of colonisation and disease, and also has the potential to facilitate novel approaches in vaccine development.Read moreRead less
Vaccine Discovery For Human Mucosal Pathogens: Identifying Novel Vaccine Antigens That Are Stably Expressed During Host Interactions, Using Analysis Of Cell-contact And Phasevarion Mediated Expression Profiles
Funder
National Health and Medical Research Council
Funding Amount
$418,482.00
Summary
The control of several human pathogens depends on vaccine development due to antibiotic resistance and the devastating outcome of infection. This work aims to identify new vaccine targets for diseases including gonorrhoae, ear infections, meningitis and sepsis, based on proteins required for interaction with human cells. Proteins that are randomly switched on and off in these bacteria will also be studied to better understand disease and to rule out variably expressed genes from new vaccines.
Characterisation Of Antigenic Variation Of Neisserial Cell Surface Adhesins, And Their Role In Infection
Funder
National Health and Medical Research Council
Funding Amount
$556,983.00
Summary
A group of bacteria called Neisseria cause human-specific infections. They produce two types of surface proteins termed adhesins, which allow the bacteria to adhere to, and invade, human cells. There is circumstantial evidence to suggest the bacteria can rapidly vary the structure of these adhesins, even within a single infection. This project will determine whether, and how, this variation is occurring, and what effect it has on the ability of the bacteria to cause disease.
Certain bacterial DNA repeats are prone to hyper mutation. Genes with these repeats, Contingency genes, are randomly switched on and off. This process, phase variation , generates diversity in a population. Recently we described a new class of contingency gene that methylates DNA. On-off switching of this gene leads to random switching of multiple genes; the phasevarion . We will define the impact of this system in bacteria causing meningitis and STDs.
Molecular Epidemiology Of Neisseria Gonorrhoeae In Different Communities In Sydney, :informing Control Measures
Funder
National Health and Medical Research Council
Funding Amount
$22,677.00
Summary
Gonorrhoea is the second most common notifiable bacterial sexually transmitted disease (STD) in Australia. This project seeks to evaluate typing methods to identify transmission patterns of different strains of gonorrhea. The molecular strain typing methods and the antimicrobial resistance surveillance outcomes employed in this study when integrated with STD control strategies will provide pragmatic and cost effective approaches whereby the enhancement of HIV spread by STIs will be curtailed.