Centre for Infectious Diseases and Microbiology
The Centre for Infectious Diseases and Microbiology (CIDM) was established in 1992 to:
- Conduct research into the pathogenesis, epidemiology and treatment of fungal, bacterial and viral diseases and translate results into improved health outcomes.
- Initiate and coordinate effective education programs in Infectious Diseases and Microbiology.
- Provide a comprehensive reference centre and resource in clinical, epidemiological and laboratory aspects of Infectious Diseases and Microbiology.
It is comprised of the following five sections.
- CIDM Biomedical Research
- CIDM Public Health
- Sexually Transmissible Infections Research Centre (STIRC)
- CIDM Clinical Services
- CIDM Laboratory Services.
The CIDM Biomedical Research section is part of the Westmead Millennium Institute. Tania Sorrell is Professor of Clinical Infectious Diseases and Director of the Centre for Infectious Diseases and Microbiology, Westmead.
CIDM Biomedical Research
The research within CIDM Biomed is directed to three main themes:
- Mycology
- Antibacterial Resistance
- New Diagnostic Platforms.
The Mycology Program includes molecular and biochemical basis of disease
caused by the fungus, Cryptococcus neoformans (the commonest cause of fungal
meningitis) and new diagnostic platforms.
In Bacteriology, we are examining
the genetic basis for antibiotic resistance and especially the nature of
transferable elements that are involved.
New diagnostic technologies are utilising the genetic targets discovered in this process to rapidly identify resistant bacteria in clinical specimens.
Bacteriology, Antibiotic Resistance, and Rapid Diagnostics
Bacterial pathogenesis
This group first characterised the genomic diversity
of a unique angiogenic intracellular bacterial pathogen (Bartonella
henselae), and was involved in the characterisation of the unique
intracellular trafficking of that pathogen. Work continues in that area,
with analysis of gene expression of intracellular bacteria.
Antibiotic resistance
Our group described the molecular bases for important
emergent carbapenem resistance in this country, its mobility and its
variable phenotype. We have extended these studies into other important
resistance genes, including those encoding resistance to the antibiotics
most significant in Intensive Care.
There are two primary objectives:
- to better understand the nature of the mosaic shared genome in
Gram-negative bacteria, in order to better understand antibiotic effects, and
- to develop real-time comprehensive surveillance tools (both in
silico and in vitro) which enable us to detect problem antibiotic resistance
in the clinical context.
Rapid diagnostics
Translation of this research requires harnessing of new
multiplexed technology (multiplexed tandem PCR) to diagnostic targets
(fungal, viral or bacterial identification and resistance genes), in
collaboration with the inventor (K Stanley, AusDiagnostics). These assays
are currently in trials and development stages in the laboratory and may
bring real-time diagnosis of serious infection to the bedside in the near
future.
Fungal Pathogenesis Research Group
A major focus of our research is to identify secretion mechanisms of pathogenic fungi. The model fungal pathogen, Cryptococcus neoformans, uses the secretory pathway to export virulence factors such as capsule building blocks and enzymes involved in stress protection and cell wall/membrane remodelling.
Our group has a particular interest in a secreted phospholipase B (PLB1) which degrades host membranes and lung surfactant, facilitating invasion/dissemination of infection within the host. We have demonstrated that PLB1 associates with fungal membranes and the cell wall via a glycosylphosphatidylinositol (GPI) anchor prior to its release from the cell surface.
Additionally, we have demonstrated that cell wall-associated PLB1 attaches specifically to beta glucan sugars that are unique to fungal cell walls, and that cell wall-associated PLB1 is a source of secreted enzyme. Our data therefore implicates beta glucanases in the release of PLB1 from the cell wall and highlights their potential as a future antifungal drug target. By using targeted gene disruption, our aim is to identify beta glucanases involved in PLB1 release from the cell surface and potentially cell wall remodelling.
We have also identified a second phospholipase-encoding gene (PLC1) contributing to fungal virulence and are investigating its mechanism of action and role in signal transduction.
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