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EU-funded researchers develop novel approach to investigate bacteria

Vaccinologists take note: British researchers have come up with a new way to investigate potentially deadly disease-causing bacteria. This fresh approach could help accelerate the process of finding vaccines. Presented in the journal PLoS ONE, the research was funded in part b...

Vaccinologists take note: British researchers have come up with a new way to investigate potentially deadly disease-causing bacteria. This fresh approach could help accelerate the process of finding vaccines. Presented in the journal PLoS ONE, the research was funded in part by the GAMEXP ('Genomic approaches to metabolite exploitation from Xenorhabdus, Photorhabus') project, which has clinched almost EUR 2.7 million under the Health Theme of the EU's Seventh Framework Programme (FP7). According to the team, which is led by the University of Exeter, not much is known about the infection biology of the Burkholderia pseudomallei (B. pseudomallei) pathogen. However, this bacterium was identified as being endemic to tropical regions, such as Southeast Asia, where it triggers a highly infectious disease called melioidosis. 'B. pseudomallei is a Gram-negative facultative intracellular pathogen that is able to replicate in macrophages,' say the authors of the study. 'However, despite the critical nature of its interaction with macrophages, few anti-macrophage factors have been characterised to date.' Dr Andrea Dowling from Exeter's Centre for Ecology and Conservation and her colleagues established a simple screen that can help isolate the virulent parts of the gene structures of B. pseudomallei. With this new method, the researchers can run a battery of tests to identify the parts of a pathogen's genetic code that help it to render immune systems ineffective. 'From there we can focus in on those key areas to find out how the pathogen works and how we can develop vaccines,' explains Dr Dowling, the lead author of the paper. 'The screen allows us to study and tackle the causes of disease and infection much quicker than other methods.' According to the team, B. pseudomallei seemingly infects people directly from the environment through cuts and grazes. Under normal circumstances, the body's immune system would absorb any invading bacteria. However, B. pseudomallei appears to spread to other parts of the body without being consumed. What emerges is a nasty infection. Thanks to their simple yet advanced screen, the team isolated the unique parts of B. pseudomallei's genetic code which could be responsible for its resistance to the human immune system. 'We used library-clones which each contain a genetic region of Burkholderia, and then studied each one's ability to kill immune cells to find what are known as virulence factors - basically the parts which allow it to override the immune system,' Dr Dowling says. 'Using the screen, we established the potential locations of that virulence factor much quicker than using normal methods. We can then study the mechanism for these factors using microbiological, cellular and biochemical techniques to see whether disrupting the virulence factor reduces the abilities of this bacteria to overcome the immune system.' Commenting on the results of this research, co-author Professor Richard Ffrench-Constant from Exeter says: 'Knowledge gained from this research provides essential insights into how this poorly understood, but extremely serious human pathogen works to cause disease, and, crucially, it helps us identify candidates for the development of much needed vaccines.' The researchers say these latest techniques will not only be good for studying B. pseudomallei but they can be used to assess other pathogens as well.For more information, please visit: University of Exeter:http://www.exeter.ac.uk/PLoS ONE:http://www.plosone.org/home.actionGAMEXP project:http://www.gamexp.eu/

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