Structural And Functional Analysis Of Glucosyltransferases (Gtr) Involved In O-antigen Modification Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$340,976.00
Summary
Shigellosis caused by Shigella flexneri is a medically significant disease in developing countries. Serotypes of S. flexneri are determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses carry the genes which confer O-antigen modification giving rise to different serotypes. The project will address fundamental processes related to the O-antigen modification by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster.
Molecular Basis Of O-antigen Modification And Genomics Of Serotype-converting Bacteriophages Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection a ....There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection and subsequent incorporation of the virus into the genetic material of the bacterial cell result in modification of the bacterial O-antigen. This phage-mediated O-antigen modification gives rise to different serotypes. The project will address fundamental processes related to the O-antigen modification. This will be achieved by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster. We have isolated several serotype-converting bacteriophages from S. flexneri and we plan to compare and characterise their genomic information to increase understanding of their origin and relationship with the bacterial host.Read moreRead less
Characterizing The Molecular Mechanisms Of Clinically Important Bacterial-fungal Interactions; The Potential To Uncover Novel Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$480,492.00
Summary
In hospitals and in nature, diverse microbes, such as bacteria and fungi, often live in close proximity to each other. Their interactions can either be helpful or detrimental to one another, and such interactions are likely important for their ability to cause human disease. This proposal aims to study the mechanisms by which bacteria interact with fungi and by doing so, will identify important mechanisms of how microbes cause human illness and also uncover new targets for antibiotic development ....In hospitals and in nature, diverse microbes, such as bacteria and fungi, often live in close proximity to each other. Their interactions can either be helpful or detrimental to one another, and such interactions are likely important for their ability to cause human disease. This proposal aims to study the mechanisms by which bacteria interact with fungi and by doing so, will identify important mechanisms of how microbes cause human illness and also uncover new targets for antibiotic development.Read moreRead less
Role Of Streptococcus Agalactiae Glyceraldehyde 3-phosphate Dehydrogenase (GAPDH) In Infection And Potential As A Target To Control Colonization In The Female Genital Tract
Funder
National Health and Medical Research Council
Funding Amount
$677,177.00
Summary
Extracellular proteins produced by pathogenic bacteria can facilitate microbial colonization of the host by mediating binding to host cells and by modulating the immune system. These proteins exert their effects by subverting specific elements of the immune system and this can allow infection to worsen. This project will increase our understanding of how this bacterium chronically colonizes humans and will identify the potential of a bacterial protein, termed GAPDH, as a target for control.
Integrated Bacterial Genomics And Virulence Analysis Of Uropathogenic Streptococcus Agalactiae
Funder
National Health and Medical Research Council
Funding Amount
$747,457.00
Summary
Urinary tract infections (UTI), which start as a bladder infection and often evolve to encompass the kidneys, are among the most common infectious diseases in humans. Streptococcus agalactiae is an important cause of gram-positive bacterial UTI. We will study the genomes and functions of specific genes in reference strains of this bacterium isolated from patients with different forms of infection to elucidate how bacterial genes and virulence factors contribute to these types of infections.
Uncovering Novel Roles Of Escherichia Coli Flagella And LPS In Uropathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$404,677.00
Summary
Urinary tract infections (UTI) are common infectious diseases in humans. Uropathogenic Escherichia coli (UPEC) cause most UTI. UPEC produce factors that promote their survival and influence disease such as flagella. We have identified anti-inflammatory responses as a key element of UTI and have shown that these responses contribute to control of UTI. In this project, we will investigate how the UPEC flagella component, FliC, contributes to anti-inflammatory responses and what this means for UTI.
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
Glycan-glycan Interactions Between Bacterial Pathogens And Host Cells: A Novel Mechanism Of Bacterial Adherence, A New Opportunity For Strategies To Treat And Prevent Disease And A New Paradigm In Interactions Between Macromolecules.
Funder
National Health and Medical Research Council
Funding Amount
$1,059,344.00
Summary
Cell surface carbohydrates are ubiquitous throughout nature. Human cell surface carbohydrates are specifically targeted by microbial proteins. These interactions are crucial in causing disease. We have recently shown that the carbohydrates on our cells and those on pathogenic bacteria can interact with one another. Understanding the nature and role of these newly discovered interactions may lead to strategies to block them via new drugs and vaccines.