Researchers dismantle one of Bacteria’s most wicked weapons: The Molecular Crossbow

Researchers from the Institut Pasteur and the National Center for Scientific Research in Paris have elucidated the molecular structure of a crossbow-like weapon from bacteria’s arsenal. Ultimately, this could help to fight infectious diseases.

Bacteria are in a constant battle with innumerable other microbes in their environment, so they have to bring in the big guns to survive. A main strategy of them is to inject virulence factors into other bacteria or cells to modify their physiology to their advantage. They do this with a complex molecular machinery, from which the precise architecture remained unknown – until the groups of Eric Cascales and Rémi Fronzes got to the bottom of it.

The machinery in focus is more specifically the bacterial type VI secretion system. The scientific team describes it as resembling a molecular crossbow that propels an arrow into the inner of the target cell, while this “crossbow” is stably attached to the bacterial envelope.

© Institut Pasteur

Using high-resolution electron microscopy, the scientists could enlighten that the crossbow-complex is assembled by the addition of three proteins, namely TssJ, TssM, and TssL. During its attachment to the target cell, a pore is formed on its membrane to enable the arrow, which is made of haemolysin co-regulated protein tube and a valine–glycine repeat protein G, to pass through.

In the long-term, the precise architecture of these secretion systems could help stop bacteria from causing health problems. Lung inflammation, Cholera, Morbus Crohn … all these diseases are triggered by bacteria that use this machinery. The researchers hope that when new drugs target specific sections of the system, they can finally block the pathogenic activity – and making the patient healthy again.

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