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Functional Biology of Bacterial Pathogens

Rood Lab photo

Research in this laboratory is centred on the molecular genetics of pathogenic anaerobic bacteria and involves five major mechanistic research themes;

All of these projects involve bacterial genetics, recombinant DNA technology, DNA sequencing, PCR technology, protein purification and other essentially molecular biological methods.

The research group is an integral part of the ARC Centre for Structural and Functional Microbial Genomics and the NHMRC Australian Bacterial Pathogenesis Program. It is part of the Monash Research Strength in Bacterial Pathogenesis. Research funding is from the ARC , NHMRC , and NIH and Australian Poultry CRC

Major collaborations involve the Department of Immunology , the Department of Biochemistry and Molecular Biology , the University of Pittsburgh , the University of Oklahoma , the University of California-Davis , the Eastman Dental Institute , the University of Sydney , The Institute for Genomic Research , University of Arizona , CSIRO Livestock Industries , Institut Pasteur , Loyola University , Ghent University and Tufts University.

Molecular analysis of clostridial transposons

Understanding bacterial antibiotic resistance mechanisms and how they are transferred is important for fighting infectious disease. This laboratory has played a leading role in determining the functional relationship of clostridial resistance determinants to those of other bacteria. The novel Tn4451 family of chloramphenicol resistance transposons from Clostridium perfringens and Clostridium difficile have been identified and characterised. These transposons are excised as a circular molecule by the large resolvase/invertase protein TnpX and can be mobilised by a process involving the TnpZ Mob protein. Current studies involve structure-function studies on the TnpX resolvase and the genetic analysis of a lincomycin resistance determinant from C. perfringens .

Recent Publications:

The biology of large clostridial plasmids

Understanding bacterial virulence and antibiotic resistance mechanisms and how these genes are transferred is important for fighting infectious disease. Earlier studies focussed on resistance genes but we are now primarily studying the conjugation mechanisms of the tetracycline resistance plasmid pCW3; as a model system for the analysis of conjugation in Clostridium perfringens. We have completely sequenced this 47-kb plamid and are in the process of identifying genes involved in conjugation. In addition, we are also studying the large toxin plasmids encoded by type B, C and D strains of C. perfringens,  with the objective of examining the genetic organisation and mobility of the toxin genes and their role in virulence.

Recent Publications:

Regulatory networks in the pathogenic clostridia

Studies in this laboratory have led to the identification and characterisation of a two-component signal transduction system (VirS/VirR) that regulates the production of several toxin genes that are involved in the pathogenesis of Clostridium perfringens -mediated gas gangrene. We have identified functional regions of the VirS and VirR proteins and have analysed the DNA binding sites of VirR. These studies show that the VirR response regulator binds to two directly repeated VirR boxes located upstream of the target gene promoters. Our current objectives are to determine the precise sequence requirements at these binding sites and to analyse the  phosphotransfer reactions and protein-protein interactions that  are involved in the transcriptional activation of VirR-regulated genes. In addition, we are also examining the role of two-component signal transduction systems in Clostridium difficile , with a focus on the regulation of toxin production by the alternative sigma factor TcdR (prev. TxeR) .

Recent Publications:

The pathogenesis of clostridial infections

The anaerobic bacterium Clostridium perfringens is the causative agent of clostridial myonecrosis or gas gangrene. The organism produces at least seventeen different extracellular enzymes and toxins, many of which are believed to be important in pathogenesis. By making isogenic chromosomal mutants in C. perfringens we have shown that the alpha-toxin is essential for virulence and that perfringolysin O has synergistic effects in the disease process. Current studies are aimed at investigating the role of other extracellular toxins in disease and at the analysis of other clostridial pathogens.

Recent Publications:

Pathogenesis, regulation and genomics of the footrot pathogen Dichelobacter nodosus

Ovine footrot is one of the most economically significant diseases of sheep in Australia. The causative agent is the anaerobic bacterium Dichelobacter nodosus. Research in this laboratory has involved the cloning and analysis of genes coding for two of the major virulence antigens, namely the fimbriae and proteases and the identification and analysis of pathogenicity islands in D. nodosus . Recently we have made a major breakthrough in D. nodosus genetics by developing a method for introducing DNA into this organism. This advancement has allowed genetic analysis in D.nodosus and more importantly the study of the virulence of D. nodosus possible. New areas of research involve utilizing reverse genetics to study the role of putative virulence factors in disease. Current studies focus on making knockout mutants of the protease structural genes and genes that are involved in fimbrial biogenesis.

Recent Publications:

Head of Research Group
Professor Julian Rood

Postdoctoral Research Fellows
Dr. Dena Lyras
Dr. Glen Carter
Dr. Ruth Kennan
Dr. Trudi Bannam
Dr. Jackie Cheung
Dr. Vicki Adams
Dr. Xiaoyan Han

Ph.D. Students
Ms. Radhika Bantwal
Mr Thomas Hiscox
Mr. Wilson Wong
Ms. Catherine Kennedy
Ms. Jenny Parsons
Ms. Kate Mackin
Ms. Lauren Stevenson
Ms. Anjana Chakravorty

Research Assistants
Ms. Milena Awad
Ms Rachael Poon
Ms. Paola Vaz

Technical Officer
Ms. Pauline Howarth

Honours Students
Ms Jocelyn Choo
Ms Jessica Wisniewski

Telephone: 03 9905 4808
Research Interests