PROJECT

Burkholderia

Identification and characterisation of virulence associated genes

 

We have a strong interest in understanding the molecular mechanisms by which bacteria cause disease. Our main focus is on the Gram-negative bacterium, Burkholderia pseudomallei, which causes the tropical disease melioidosis. The disease is thought to be endemic in at least 45 countries worldwide, and has a predicted global burden of approximately 165,000 cases, of which 89,000 were fatal in the past year. Even with effective antibiotic treatment, mortality rates of melioidosis in Northern Australia are approximately 15 per cent.

B.pseudomallei is also intrinsically resistant to many classes of antibiotics, therefore the development of novel medical countermeasures is of high priority. We have identified several virulence factors which enable B. pseudomallei to cause disease and are currently collaborating with international partners to identify novel inhibitors.

 

Project goal

Identification and characterisation of anti-virulence associated proteins in Burkholderia pseudomallei.

Funding

 

We acknowledge the following partners for their generous funding:

Defence Materials Technology Centre, Australia
NATO (North Atlantic Treaty Organisation) Science for Peace and Security
Defence Science Technology Laboratory

 

DMTC logo     NATO logo      DSTL logo

Collaboration

 

  • Professor Tim Atkins, Defence Science Technology Laboratory, UK
  • Professor Charlie Bond, UWA, Perth
  • Professor Ulrike Holzgrabe, University of Wurzburg, Germany
  • Dr Charlene Kahler, UWA, Perth
  • Professor Peter Myler, SSGCID, Seattle
  • Dr Hayley Newton, Doherty Institute, Melbourne
  • Professor Alice Vrielink, UWA, Perth

 

Recommended reading

The following readings relate to this project:

 

  • Norville IH, Harmer NJ, Harding SV, Fischer G, Keith KE, Brown KA, Sarkar-Tyson M, Titball RW. (2011). A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects on virulence. Infect Immun. 2011 Nov;79(11):4299-307.
  • Norville IH, Breitbach K, Eske-Pogodda K, Harmer NJ, Sarkar-Tyson M, Titball RW, Steinmetz I. (2011). A novel FK-506-binding-like protein that lacks peptidyl-prolyl isomerase activity is involved in intracellular infection and in vivo virulence of Burkholderia pseudomallei. Microbiology. 157(Pt 9):2629-38.
  • Norville IH, O'Shea K, Sarkar-Tyson M, Zheng S, Titball RW, Varani G, Harmer NJ. (2011). The structure of a Burkholderia pseudomallei immunophilin-inhibitor complex reveals new approaches to antimicrobial development. Biochem J. 437(3):413-22.
  • Southern SJ, Scott AE, Jenner DC, Ireland PM, Norville IH, Sarkar-Tyson M. (2016). Survival protein A is essential for virulence in Yersinia pestis. Microb Pathog. 2016 Mar;92:50-3.
  • Seufert, F., Kuhn, M., Hein, M., Weiwad, M., Vivoli, M., Norville, I., Sarkar-Tyson, M., Marshall, L., Schweimer, K., Bruhn, H., Rösch, P., Harmer, N., Sotriffer, C., Holzgrabe, U. 2016, 'Development, synthesis and structure–activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei', BIOORGANIC & MEDICINAL CHEMISTRY, 24, 21, pp. 5134-5147
  • Custódio, R., Mclean, C., Scott, A., Lowther, J., Kennedy, A., Clarke, D., Campopiano, D., Sarkar-Tyson, M., Brown, A. 2016, 'Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei', MOLECULAR MICROBIOLOGY, 102, 6, pp. 1004-1019. 
  • Vanaporn, M., Sarkar-Tyson, M., Kovacs-Simon, A., Ireland, P., Pumirat, P., Korbsrisate, S., Titball, R., Butt, A. 2016, 'Trehalase plays a role in macrophage colonization and virulence of Burkholderia pseudomallei in insect and mammalian hosts', Virulence, 8, 1, pp. 30-40. 
  • Southern, S., Male, A., Milne, T., Sarkar-Tyson, M., Tavassoli, A., Oyston, P. 2015, 'Evaluating the role of phage-shock protein A in Burkholderia pseudomallei', MICROBIOLOGY-SGM, 161, 11, pp. 2192-2203. 
  • Ireland, P., Marshall, L., Norville, I., Sarkar-Tyson, M. 2014, 'The serine protease inhibitor Ecotin is required for full virilence of Burkholderia pseudomallei', MICROBIAL PATHOGENESIS, 67-68, pp. 55-58. 
  • David, J., Sayer, N., Sarkar-Tyson, M. 2014, 'The use of a three-dimensional cell culture model to investigate host-pathogen interactions of Francisella tularensis in human lung epithelial cells', MICROBES AND INFECTION, 16, pp. 735-745. 
  • Nandi, T., Holden, M., Didelot, X., Mehershahi, K., Boddey, J., Beacham, I., Peak, I., Harting, J., Baybayan, P., Guo, Y., Wang, S., How, L., Sim, B., Essex-Lopresti, A., Sarkar-Tyson, M., Nelson, M., Smither, S., Ong, C., Aw, L., Hoon, C., Michell, S., Studholme, D., Titball, R., Chen, S., Parkhill, J., Tan, P. 2014, 'Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory and epigenetic profiles', GENOME RESEARCH, 25, pp. 129-141. 

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Contact

PhD opportunities investigating the immune response to Burkholderia pseudomallei using cell infection models are available. Get in touch for more information.