Bacterial injection needle structure decoded
Scientists in Germany and the United States have decoded the structure of bacterial injection needles at atomic resolution. Presented in the journal Nature, the results of the study could help researchers create tailor-made drugs and develop strategies that specifically prevent the process of infection. Bacteria-triggered diseases are dangerous because their host is infected via an injection apparatus. The study was funded in part by the BIO-NMR ('Nuclear magnetic resonance (NMR) for structural biology') project, which has secured almost EUR 9 million under Research Infrastructures of the EU's Seventh Framework Programme (FP7). Led by the Max Planck Institute for Biophysical Chemistry in Germany, researchers say bacteria release molecular agents into their host cell through needle-like structures. This way, they are able to avoid the immune response. Through their work, they deciphered the structure of this needle, finding that hundreds of small hollow needles pop out of the bacterial membrane, making it a dangerous tool that is responsible for making plague or cholera so dangerous. The tiny needles, working along with a base that is found inside the membrane, comprise what experts call the type III secretion system, which is an injection device through which the pathogens introduce molecular agents into their host cell. The substances then influence essential metabolic processes and immobilise the immune defence of the infected cells, according to the researchers. The end result? Death, as the pathogens make their way throughout the organism, successfully dodging anything that tries to stop them. Researchers until now have only succeeded in prescribing medication that can fight infection. But bacterial strains able to develop resistance to antibiotics exist. So the research world needs to develop more specific drug treatments. No one has been able to provide insight on the specific structure of the 60 to 80-nanometre-long and some 8-nanometre-wide needles. Conventional tools like X-ray crystallography or electron microscopy failed or yielded wrong model structures. The needle, because it is not crystallisable and insoluble, resisted all attempts to decode its atomic structure. Enter this research team that combined the production of the needle in the laboratory with solid-state NMR spectroscopy, electron microscopy and computer modelling. They decoded the structure of the needle atom by atom and imagined its molecular architecture for the first time in the angstrom range. Experts say this is a resolution of less than a tenth of a millionth of a millimetre. 'We have made big steps forward concerning sample production as well as solid-state NMR spectroscopy,' says lead author Adam Lange from the Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry. 'Finally, we were also able to use one of the presently most powerful solid-state NMR spectrometers in Christian Griesinger's NMR-based Structural Biology Department at our institute.' With 20 tesla, the magnetic field of this 850 megahertz spectrometer is about 400,000 times as strong as that of the Earth. 'We were surprised to see how the needles are constructed,' says Dr Lange. Their results show similarities inside the needles but differences on the surface. This difference could be what the bacteria use to evade immune recognition by the host. Changes on the needles' surface play havoc with the immune system of the host because the latter cannot recognise the pathogen. Their work could help researchers block the syringe system and keep bacteria in check. 'Thanks to our new technique, we can produce large amounts of needles in the lab,' says Stefan Becker, also from the Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry and one of the authors of the study. 'Our aim is now to develop a high-throughput method. This will allow us to search for new agents that prevent the formation of the needle.' Experts from the Max Planck Institute for Infection Biology in Germany and the University of Washington in the United States contributed to this study.For more information, please visit:Max Planck Institute for Biophysical Chemistry:http://www.mpibpc.mpg.de/english/start/index.phpNature:http://www.nature.com/
Countries
Germany, United States