Black Death Genomics And The Evolution Of Pathogen Virulence
Funder
National Health and Medical Research Council
Funding Amount
$525,412.00
Summary
The Black Death was one of the most lethal plagues of antiquity and changed the course of human history. We will reconstruct and analyse the evolution of its causative agent – the bacterium Yersinia pestis – sampled from human skeletal remains dating back to the Black Death and beyond. We will determine the mutations that changed the virulence of plague epidemics through time, enabling a unique insight into the most dramatic example of pathogen emergence that has ever been available for study.
Pathogenesis Of Infections With Yersinia Enterocolitica
Funder
National Health and Medical Research Council
Funding Amount
$339,634.00
Summary
Yersinia enterocolitica is a significant cause of food-poisoning, gastroenteritis and abdominal pain which may be mistaken for acute appendicitis. Y. enterocolitica is a heterogenous bacterial species only some strains of which are able to cause disease. Many of the disease-causing strains have readily identifiable virulence determinants which facilitate their detection in clinical microbiological laboratories. By contrast, other types, in particular the biotype 1A strains, lack these determinan ....Yersinia enterocolitica is a significant cause of food-poisoning, gastroenteritis and abdominal pain which may be mistaken for acute appendicitis. Y. enterocolitica is a heterogenous bacterial species only some strains of which are able to cause disease. Many of the disease-causing strains have readily identifiable virulence determinants which facilitate their detection in clinical microbiological laboratories. By contrast, other types, in particular the biotype 1A strains, lack these determinants, although many of them are significantly associated with disease. During the past few years, we have compared biotype 1A strains of Y. enterocolitica obtained from patients with those from non-clinical sources in a number of assays for virulence-associated properties. These studies have shown that clinical isolates differ from non-clinical ones in terms of their ability to (1) invade epithelial cells in vitro and intestinal absorptive cells in vivo, (2) escape from epithelial cells and macrophages they have invaded, (3) resist killing by macrophages, and (4) colonise the intestinal tracts of mice. The aim of the study is to identify the bacterial determinants responsible for these differences between clinical and non-clinical strains of Y. enterocolitica biotype 1A. This will be achieved by using genetic techniques to modify virulent strains of biotype 1A at random and then identify derivatives of these bacteria with altered virulence properties. We shall also use genetic techniques to identify genes that are specifically activated when the bacteria come into contact with animal cells and tissues. The results of this research will provide new insights into the virulence mechanisms of Y. enterocolitica and related bacteria, and will be used to develop diagnostic tests which will allow pathogenic strains to be distinguished from harmless ones.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.
Characterising The Role Of IL-37 In The Development Of H. Pylori Infection.
Funder
National Health and Medical Research Council
Funding Amount
$641,992.00
Summary
H. pylori infects more than 50% of the worlds population and is the causative agent of gastric cancer, the second leading cause of cancer-related deaths worldwide. Infection with H. pylori occurs during early childhood and persists within the host for life, causing immune suppression and therefore preventing clearance of the infection from the individual. We will examine a newly identified mechanism of H. pylori-induced immune suppression in humans in an attempt to provide novel treatments.
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.
Functional Characterisation Of The Malaria Protein Export Machinery
Funder
National Health and Medical Research Council
Funding Amount
$556,104.00
Summary
The ability of malaria parasites to cause one of the most devastating infectious diseases of humans is in part due to their ability to export hundreds of proteins into their host red blood cells to obtain nutrients, evade the immune system and contribute to associated pathologies. Recently, we discovered the molecular machine that exports proteins into the host cell and so now we wish to establish how it works so that drugs can be tailored to block it to kill these parasites.
Microbial Involvement In The Development Of Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
Despite extensive research investigating the causative agent(s) of Inflammatory Bowel Disease (IBD), the results of current studies remain inconclusive. One reason for this relates to study design and the sensitivity of techniques used. This project will investigate differences in the microbial composition and metabolic profiles of newly diagnosed IBD children as compared with matched controls. If successful, these results will provide insights into possible aetiological agent(s) of IBD.