Faculty of Medicine, Dentistry and Health Sciences Department of Microbiology and Immunology

Strugnell Laboratory

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Include: Research Interests | Major Research Projects | Laboratory Staff | Recent Publications | Links

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Research Interests

The Laboratory is interested in how bacteria cause disease and what interventions can be made to stop this happening.

The research is therefore focussed into two areas – firstly, the bacterial products and strategies that allow the organism to avoid being destroyed by the mammalian immune system, and secondly, the types of immune responses that can circumvent these strategies and products.

The product of this research is captured in the development of novel vaccines.

Major Research Projects

The bacteria under investigation are:

Each of these bacteria has a different relationship with its mammalian host.

Salmonella typhimurium is an intracellular bacterium that replicates with macrophages, specialised cells designed to ‘clean' the blood of pathogenic organisms. The intracellular location means that many antibiotics are ineffective, and vaccines dependent on T lymphocytes are important to host resistance to reinfection. We are currently examining how the bacterium can persist inside cells like macrophages and the metabolic processes the bacterium uses to facilitate intracellular replication; Our experience in manipulating Salmonella and its use in vaccination against Salmonella disease, and as a ‘vector' for vaccination against unrelated pathogens, has been exploited in the search for new human vaccines.

Helicobacter pylori is perhaps the world's commonest pathogen causing disease in almost half the world's population. This disease can be serious (e.g. stomach cancer) or benign like a chronically upset stomach. H. pylori lives in the hostile environment of the stomach and burrows into the mucous that protects the stomach lining against the ravages of the acid and enzymes released to degrade food. Once in the mucous it releases factors which cause a chronic inflammation of the stomach and attracts white blood cells. The movement of lymphocytes and granulocytes into the stomach leads to symptomatic or asymptomatic disease. We are currently trying to understand the role of T lymphocytes in the chronic, precancerous condition known as gastritis.

Klebsiella pneumoniae is a neglected bacterial pathogen of importance to elderly, hospitalised patients in eg. ICUs where it causes wound and urinary tract infections. The bacterium is heavily encapsulated, appears to reside extracellularly and grows rapidly in the blood. The genome of this bacterium is relatively large and contains many functionally undefined genes. The studies we are undertaking are aimed at elucidating the processes leading to infection, disease and immunity in small animal models. These studies are directed at defining the role(s) of lipopolysaccharide, iron, conserved membrane proteins and the variable carbohydrate antigens produced by this bacterium in the pathogenesis of K. pneumoniae disease.

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Collaborators (NHMRC- Bacterial Pathogenesis Grant):

Roy Robins-Browne
Mike Jennings

Other Collaborators:

Per Brandtzaeg
Roy Curtiss III
Andrew Giraud
Christopher Sobey

Laboratory Staff

Laboratory Heads

Prof. Richard Strugnell (CRC-VT)
Dr. Odilia Wijburg (CRC-VT)

Senior Research Officers

Dr. Jaci Farn (CRC-VT)
Dr. Anna Walduck
Dr. Ji Yang

Research Assistant and Laboratory Manager

Ms. Kim Simpfendorfer

PhD Students

Mr. Raju Mantena
Ms. Abigail Clements (CRC-VT)
Dr. Adam Jenney (CRC-VT)
Ms. Mai Ping Tan (CRC-VT)
Mr. Jonathan Wilksch

Honours Students

Mr. Ho Chow
Ms. Kate Mason

Administration Support

Ms. Helen Cain (CRC-VT)

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Recent Publications: 2007 - Present

List of Publications prior to 2007

  1. Yang J, Hart E, Atanaskovic M, Price G, Hartland E, Strugnell R, Robins-Browne R. Bicarbonate-mediated transcriptional activation of divergent operons by the virulence regulatory protein, RegA, from Citrobacter rodentium. Molecular Microbiology 2008; 68: 314-27.
  2. Tan MP, Pedersen J, Zhan Y, Lew A, Pearse M, Wijburg O, Strugnell R. CD8+ T cells are associated with severe gastritis in Helicobacter pylori-infected mice in the absence of CD4+ T cells. Infection and Immunity 2008; 76: 1289-1297.
  3. Gaboriaud F, Gee ML, Strugnell R, Duval JFL. Coupled Electrostatic, Hydrodynamic, and Mechanical Properties of Bacterial Interfaces in Aqueous Media. Langmuir 2008; 24: 10988-95.
  4. Gahan M, Webster DE, Wijburg O, Wesselingh SL, Strugnell R. Impact of prior immunological exposure on vaccine delivery by Salmonella enterica serovar Typhimurium. Vaccine 2008; 26: 6212-6220.
  5. Walduck A, Kaparakis M, Price JD, van Rooijen N, Pedersen JS, Pearse MJ, Wijburg O, Strugnell R. Macrophages are mediators of gastritis in acute Helicobacter pylori Infection in C57BL/6 Mice. Infection and Immunity 2008; 76: 2235-2239.
  6. Cunningham K, Carey A, Fannie J, Bao S, Coon C, Jones R, Wijburg O, Strugnell R, Timms P, Beagley K. Poly-immunoglobulin receptor-mediated transport of IgA into the male genital tract is important for clearance of Chlamydia muridarum infection. American Journal of Reproductive Immunology 2008; 60: 405-414.
  7. Mantena RKR, Wijburg O, Vindurampulle C, Bennett-Wood V, Walduck A, Drummond G, Davies J, Robins-Browne R, Strugnell R. Reactive oxygen species are the major antibacterials against Salmonella Typhimurium purine auxotrophs in the phagosome of RAW 264.7 cells. Cellular Microbiology 2008; 10: 1058-1073.
  8. Gaboriaud F, Parcha S, Gee M, Holden J, Strugnell R. Spatially resolved force spectroscopy of bacterial surfaces using force-volume imaging. Colloids and Surfaces B: Biointerfaces 2008; 62: 206-213.
  9. Clements A, Jenney A, Gabbe J, Brown L, Deliyannis G, Hartland E, Pearse M, Maloney M, Wesselingh S, Wijburg O, Strugnell R. Targeting subcapsular antigens for prevention of Klebsiella pneumoniae infections. Vaccine 2008; 26: 5649-53.
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  10. Clements A, Gaboriaud F, Duval JFL, Gabbe J, Jenney A, Lithgow T, Wijburg O, Hartland E, Strugnell R. The major surface-associated saccharides of Klebsiella pneumoniae contribute to host cell association. PLoS One 2008; 3: 1-10.
  11. Tan MP, Kaparakis M, Galic M, Pedersen J, Pearse M, Wijburg O, Janssen P, Strugnell R. Chronic Helicobacter pylori infection does not significantly alter the microbiota of the murine stomach. Applied and Environmental Microbiology 2007; 73: 1010-1013.
  12. Price JD, Simpfendorfer KR, Mantena RKR, Holden J, Heath W, van Rooijen N, Strugnell R, Wijburg O. Gamma Interferon-Independent Effects of Interleukin-12 on Immunity to Salmonella enterica Serovar Typhimurium Infection and Immunity 2007; 75: 5753-5762.
  13. Gahan M, Webster E, Wesselingh L, Strugnell R. Impact of plasmid stability on oral DNA delivery by Salmonella enterica serovar Typhimurium. Vaccine 2007; 25: 1476-83.
  14. Mantena RKR, Wijburg O, Vindurampulle C, Bennett-Wood V, Walduck A, Drummond G, Davies J, Robins-Browne R, Strugnell R. Reactive oxygen species are the major antibacterials against Salmonella Typhimurium ppurine auxotrophs in the phagosome of RAW 264.7 cells. Cellular Microbiology 2007 10: 1-16.
  15. Clements A, Tull D, Jenney A, Gabbe J, Kim S-H, Bishop R, McPhee J, Hancock R, Hartland E, Strugnell R, McConville M, Jackson D, Wijburg O, Pearse M. Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides. Journal of Biological Chemistry 2007; 282: 15569-15577.
  16. Sait LC, Galic M, Price JD, Simpfendorfer K, Diavatopoulos D, Uren T, Janssen P, Wijburg O, Strugnell R. Secretory antibodies reduce systemic antibody responses against the gastrointestinal commensal flora . International Immunology 2007; 19: 257-265.
  17. Yang J, Baldi D, Atanaskovic M, Strugnell R, Robins-Browne R. Transcriptional regulation of the yghJ-pppA-yghG-gspCDEFGHIJKLM cluster, encoding the Type II secretion pathway in enterotoxigenic Escherichia coli. Journal of Bacteriology 2007; 189: 142-150.

 

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