Robins-Browne Laboratory
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Include: Research Interests | Collaborative Research | Funding | Some recent findings - Enteropathogenic Escherichia coli - Group A Streptococcus | Laboratory Staff | Selected Recent Publications
Research Interests
The major focus of our research is the molecular pathogenesis of bacterial infections. We use molecular biological, genetic, proteomic, and cell biological approaches to gain insight into the processes by which pathogenic bacteria interact with their hosts. The bacteria we use as model pathogens for this research are diarrhoea-causing strains of Escherichia coli, in particular enteropathogenic E. coli. We also work with group A streptococci, Streptococcus pneumoniae and Pseudomonas aeruginosa amongst others.
The principal goals of our work are to improve understanding of the strategies that bacteria employ to cause disease, and to use this information to improve current methods to diagnose, treat and prevent bacterial infections.
Collaborative research
In addition to our laboratories in the Department of Microbiology and Immunology,
we have laboratories at the Murdoch Childrens Research Institute
(www.mcri.edu.au)
located at the Royal Children's Hospital (www.rch.org.au),
where we undertake collaborative research with a number of hospital-based scientists and clinicians on
topics as diverse as:
- “The use of microarray to investigate susceptibility to and pathogenesis of infections” (with Professor Nigel Curtis)
- “Detection of carriers of Streptococcus pneumoniae” (with Professor Kim Mulholland, Dr Catherine Satzke and others)
- “The use of lactobacilli to modulate immune responses in neonates” (with Assoc Prof Mimi Tang)
- “Antibiotic susceptibility testing of bacteria from children with cystic fibrosis” (with Professor Colin Robertson and Assoc Prof John Massey)
Funding
Funding for our research comes mainly from the Australian National Health & Medical Research Council and the Australian Research Council. We also have research contracts with Bionic Technologies Australia, the Gates Grand Challenges in Global Health Fund and CSIRO amongst others.
Some recent findings
Enteropathogenic Escherichia coli
Enteropathogenic E. coli (EPEC) is a leading cause of acute diarrhoea in children worldwide. We have shown that EPEC is also an important cause of persistent diarrhoea in children attending hospital in Melbourne. As part of our work on the pathogenesis of infections caused by EPEC, we have identified a protein export pathway in EPEC that is identical to that used by enterotoxigenic strains of E. coli to secrete heat-labile enterotoxin. Although EPEC secretes no known toxins, it appears to require the protein secretory pathway to produce biofilms and to persist in the gastrointestinal tract. We have also identified two novel gene regulatory systems in EPEC and related bacteria which are essential for virulence. One of these systems responds to bicarbonate ions, whilst the other is linked to the uptake of inorganic phosphate.
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| Photomicrographs showing that enteropathogenic E. coli (arrow) which attach to epithelial cells (left) cause actin to accumulate at the site of attachment (right). | |
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| Destruction of microvilli on the surface of the intestine by enteropathogenic E. coli (arrow). | |
Group A Streptococcus
The Group A Streptococcus (GAS) is an important human pathogen that is responsible for more than 500,000 deaths worldwide each year. Australian Aborigines and Pacific Islanders are particularly susceptible to infection with GAS and its complications, including acute rheumatic fever. The most important virulence determinant of GAS is a surface antigen, known as the M-protein, which acts both as an adhesin and an antiphagocytic factor . Evidence for the central role played by M-protein in systemic GAS infection includes the observations that strains which do not produce this protein are avirulent, and that antibodies to M-protein confer type-specific immunity to infection. Because of this, M-protein is the favourite target for most investigators developing GAS vaccines. However, we have identified highly virulent strains of GAS that do not express M-protein. We are currently investigating the virulence mechanisms of these bacteria, which are intrinsically resistant to vaccines based on M-protein, to determine immunisation strategies that may be needed to control them.
Laboratory Staff
Laboratory Head and Head of Department
Professor Roy Robins-Browne
Email:r.browne@unimelb.edu.au
Current staff
Thakshila Amarasena, Technical assistant
Kristy Azzopardi, Research assistant
Dr Debbie Baldi, Postdoctoral scientist
Vicki Bennett-Wood, Research assistant
Susie Germano, Research assistant
Dr Emily Hart, Postdoctoral scientist
Danijela Krmek, Technical assistant
Frances Oppedisano, Research assistant
Dr Judyta Praszkier, Postdoctoral scientist
Dr Catherine Satzke, Postdoctoral scientist
Dr Marija Tauschek, Postdoctoral scientist
Dr Ji Yang, Postdoctoral scientist
Current students
Catherine Cheng, PhD student
Ellen Higginson, PhD student
Dianna Hocking, PhD student
Dr Nicole Ritz†, PhD student
Joel Selkrig†, PhD student
Aimee Tan, PhD student
Dr Marc Tebruegge†, PhD student
Ben Forbes, Honours student
† based off campus
Recent Publications: 2007 - Present
List of Publications prior to 2007
- Bryant P, Robins-Browne R, Carapetis J, Curtis R. Some of the people, some of the time susceptibility to acute rheumatic fever. Circulation 2009; 119: 742-753.
- Tennant S, Atanaskovic M, Azzopardi K, Bigham A, Bennett-Wood V, Hartland E, Qi W, Whittam T, Robins-Browne R. Characterisation of atypical enteropathogenic E. coli strains of clinical origin. BMC Microbiology 2009; 3: 117-127.
- Cheng C, Tennant S, Azzopardi K, Bennett-Wood V, Hartland E, Robins-Browne R, Atanaskovi M. Contribution of the pst-phoU operon to cell adherence by atypical enteropathogenic Escherichia coli and the virulence of Citrobacter rodentium. Infection and Immunity 2009; 77: 1936-1944.
- Bryant P, Smyth G, Robins-Browne R, Curtis R. Detection of gene expression in an individual cell type within a cell mixture using microarray analysis. PLoS One 2009; 4: 1-10.
- Hart E, Tauschek M, Bennett-Wood V, Hartland E, Robins-Browne R. Rabbit-specific fimbriae, Ral, alter the patterns of in vitro adherence and intestinal colonisation of rabbits by human-specific enteropathogenic E. coli. Microbes and Infection 2009; 11: 803-810.
- Robins-Browne R. ShigaToxin-producing Escherichia coli strains negative for locus of enterocyte effacement. Emerging Infectious Diseases 2009; 15: 372-380.
- Ritz N, Tebruegge M, Connell T, Sievers A, Robins-Browne R, Curtis R. Susceptibility of Mycobacterium bovis BCG vaccine strains to antituberculous antibiotics. Antimicrobial Agents and Chemotherapy 2009; 53: 316-318.
- Levine MM, Robins-Browne RM. Vaccines, global health and social equity. Immunol Cell Biol 2009; 87: 274-278.
- Bryant PA, Smyth G, Robins-Browne R, Curtis N. Global gene expression analysis of a cell mixture detects the genes in a cell subset most differentially expressed in response to a stimulus. PLoS ONE 2009; in press.
- Lahtinen SJ, Boyle RJ, Kivivuori S, Oppedisano F, Smith KR, Robins-Browne R, Salminen SJ, Tang MLK. Prenatal probiotic administration can influence Bifidobacterium microbiota development in infants at high risk of allergy. J Allergy Clin Immunol 2009; 123: 499-501.
- Newton HJ, Sloan J, Bulach DM, Seemann T, Allison CC, Tauschek M, Robins-Browne RM, Paton JC, Whittam TS, Paton AW, Hartland EL. The emergence of LEE-negative Shiga toxin producing Escherichia coli: clonal structure and acquisition of the large virulence plasmid, pO113. Emerg Infect Dis 2009; in press.
- Ritz N, Tebruegge M, Connell TG, Robins-Browne R, Curtis N. Susceptibility of BCG vaccine strains to antituberculous antibiotics. Antimicrog Ag Chemother 2009; 53: 316-318.
- Hart E, Yang J, Kelly M, Tauschek M, Frankel G, Hartland EL, Robins-Browne RM. RegA, an AraC-like transcriptional regulator is an essential virulence determinant of Citrobacter rodentium. Infect Immun 2008; 76: 5247-5256.
- Commons R, Rogers S, Gooding T, Danchin M, Carapetis J, Robins-Browne R, Curtis N. Superantigen genes in group A streptococcal isolates and their relationship with emm types. J Med Microbiol 2008; 57: 1238-1246.
- Ritz N, Hanekom WA, Robins-Browne R, Britton W, Curtis N. The influence of BCG vaccine strain on the immune response and protective immunity to tuberculosis: could protection against tuberculosis be improved by using the optimal BCG vaccine strain? FEMS Microbiol Rev 2008; 32: 821-841.
- Yang J, Hart E, Tauschek M, Price GD, Hartland EL, Strugnell RA, Robins-Browne RM. Bicarbonate-mediated transcriptional activation of divergent operons by the virulence regulatory protein, RegA, from Citrobacter rodentium. Mol Microbiol 2008; 68: 314–327.
- Leotta GA, Miliwebsky ES, Chinen I, Espinosa EM,Azzopardi K, Tennant S, Robins-Browne R, Rivas M. Characterisation of Shiga toxin-producing Escherichia coli O157:H7 strains isolated from humans in Argentina, Australia and New Zealand. BMC Microbiol 2008; 2008, 8:46.
- Lee SF, Luck SN, Kelly M, McAlister A, Robins-Browne RM, Frankel G, Hartland EL. A C-terminal class I PDZ binding motif of NleA/EspI modulates the virulence of attaching and effacing Escherichia coli and Citrobacter rodentium. Cell Microbiol 2008; 10: 499-513.
- Wei BPC, Robins-Browne RM, Shepherd RK, Clark GM, O'Leary SJ. Current concepts: pneumococcal meningitis and cochlear implantation; risk assessment and prevention. Clin Infect Dis 2008; 46: e1-7.
- Tennant SM, Hartland EL, Phumoonna T, Lyras D, Rood JI, Robins-Browne RM, van Driel IR. The influence of gastric acid on the susceptibility to infection with ingested bacterial pathogens. Infect Immun 2008; 76: 639-645.
Robins-Browne laboratory members 2008-09.