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.
Transposable Element Mobility And Chromosomal Rearrangement In The Fungal Pathogen Cryptococcus During Human Infection
Funder
National Health and Medical Research Council
Funding Amount
$322,028.00
Summary
Pathogenic fungi present in the environment have emerged as an increasingly common threat to human health. Cryptococcus neoformans and the closely related species Cryptococcus gattii are the leading causes of life-threatening fungal meningitis, and Australia is one of the few countries where both species are prevalent. Although C. neoformans is an increasingly common cause of infection in immunocompromised patients such as those suffering from AIDS, approximately one in four infected individuals ....Pathogenic fungi present in the environment have emerged as an increasingly common threat to human health. Cryptococcus neoformans and the closely related species Cryptococcus gattii are the leading causes of life-threatening fungal meningitis, and Australia is one of the few countries where both species are prevalent. Although C. neoformans is an increasingly common cause of infection in immunocompromised patients such as those suffering from AIDS, approximately one in four infected individuals has no apparent immune system defect. For patients with AIDS, in the absence of antiretroviral therapy cryptococcal infection is incurable and requires lifelong treatment with antifungal medication to keep the infection in check. During infection, Cryptococcus is under tremendous stress enforced not only by the immune system and the presence of antifungals, but also by the high temperature, nutrient limiting environment encountered in the host. The proposed research will reveal how Cryptococcus evolves in this environment to enable persistence of infection despite medical intervention. I propose that naturally occurring mobile genetic elements present in the Cryptococcus genome cause chromosomal rearrangements during long term infection to produce gene deletions and duplications that facilitate survival. By characterising these changes and the genes associated with them, the research will identify novel genes involved in pathogenesis and will increase our understanding of the infection process. The expected outcome of this project is a detailed understanding of the roles mobile element movement and chromosomal rearrangement play in Cryptococcus during infection, and how these affect genes that contribute to the pathogenic process. The fundamental knowledge gained from this study will facilitate studies designed to combat infections in the clinical setting, provide new drug targets and help foster the development of more effective therapies.Read moreRead less