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 of which CIDM Biomedical Research is part of the Westmead Millennium Institute -

CIDM Biomedical Research
CIDM Public Health
Sexually Transmissible Infections Research Centre (STIRC)
CIDM Clinical Services
CIDM Laboratory Services.

Tania Sorrell is Professor of Clinical Infectious Diseases and Director of the Centre for Infectious Diseases and Microbiology, the University of Sydney at 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 platforms are utilising the genetic targets discovered in this process to rapidly identify resistant bacteria in clinical specimens.

Research Group	Theme	Contact
Antifungal Drug Development Group	Mycology	Professor Tania Sorrell T +61 2 9845 6012 F +61 2 9891 5317 E tania_sorrell@wmi.usyd.edu.au Dr Katrina Jolliffe (Chemistry, USyd) T +61 2 9351 2297 F +61 2 9351 3329 E jolliffe@chem.usyd.edu.au Dr Fred Widmer (CIDM Biomed) T +61 2 9845 7863 F +61 2 9891 5317 E fredw@icpmr.wsahs.nsw.gov.au
Bacteriology, Antibiotic Resistance, and Rapid Diagnostics	Bacteriology	Dr Jon Iredell T +61 2 9845 6255 F +61 2 9891 5317 E joni@icpmr.wsahs.nsw.gov.au Dr Sally Partridge T +61 2 9845 6278 F +61 2 9891 5317 E sallyp@icpmr.wsahs.nsw.gov.au
Fungal Pathogenesis Research Group	Mycology	Dr Julianne Djordjevic T +61 2 9845 7367 F +61 2 9891 5317 E julie_djordjevic@wmi.usyd.edu.au
Molecular Mycology Research Laboratory	Mycology	A/Prof Wieland Meyer T +61 9845 6895 F +61 2 9891 5317 E w.meyer@usyd.edu.au
New Fungal Diagnostics	Mycology	Professor Tania Sorrell T +61 2 9845 6012 F +61 2 9891 5317 E tania_sorrell@wmi.usyd.edu.au

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;
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.