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Chlamydia study leads to better understanding of bacterial infection mechanisms

Molecular nano machines act like mini-syringes when infecting host cells

New research into the molecular structure of the sexually-transmitted Chlamydia bacterium has revealed important information about an infection mechanism underlying many bacterial diseases worldwide.

Using a specific electron microscopy technique, the team of London-based researchers have observed molecular nano machines on the surface of the bacteria acting like mini-syringes that compact to propel their infectious cargo into cells of their human hosts.

As these nano machines ­- a ‘type III secretion system’ (T3SS) - are present in a spectrum of disease-causing bacteria such as Salmonella, some E.coli, Shigella that causes dysentery and Yersinia that causes plague, it is expected this study will help in the development of compounds to target and inhibit them in the future.

The study, published today in Nature Communications and funded by the Wellcome Trust, has been carried out at the Institute of Structural and Molecular Biology – a joint centre of research linking the Department of Biological Sciences at Birkbeck, University of London, and the Department of Structural and Molecular Biology at University College London (UCL).

The research team, led by Dr Richard Hayward and Professor Helen Saibil, studied the structure of the T3SS found in Chlamydia trachomatis, the bacterium that causes sexually transmitted disease and a particular form of blindness called trachoma in developing nations.

The researchers used cryo-electron tomography (cryo-ET) an electron microscopy technique applied to obtain detailed three-dimensional structures of macromolecular complexes in cells.

Explaining the outcomes of the study, Dr Hayward said: “Our findings reveal that the chlamydial T3SS, while sharing key features known in other bacterial secretion systems, looks strikingly different.“

“The cryo-ET technique also allowed us to visualise the T3SS in contact with a host cell membrane for the first time. By examining molecular complexes in the cell-free and cell-associated state and comparing the differences between them, we revealed remarkable ‘pump-action’ structural changes that allow effector injection into the cell, suggesting that T3SSs act like mini-syringes.”

Discussing the potential implications of this study, he added: “Understanding further detail about how these T3SSs work is very important as it might allow the development of compounds to target and inhibit them, thus preventing a spectrum of bacterial diseases. This is now especially important given the increasing incidence of resistance to antibiotics.”

The study, "Structure of a bacterial type III secretion system in contact with a host membrane in situ” has been published in Nature Communications

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