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Bacterial injection needle could lead to new drugs

Structural Biology - New research on the composition and structure of a needle-like protein on the surface of bacteria may help scientists develop new strategies to thwart infection.

A team from the US say a needle-like protein complex - known as a type III secretion system (or T3SS) - on the surface of Shigella bacteria is a complex protein structure that traverses the bacterial cell membrane and acts as a biological syringe to inject deadly proteins into intestinal cells.

These proteins rupture the cell's innards, leading to bloody diarrhea and sometimes death. Similar secretion systems exist in a range of other infectious bacteria, including those that cause typhoid fever, some types of food poisoning, and plague.

"Understanding the 3D structure of these secretion proteins is important for the design of new broad-spectrum strategies to combat bacterial infections," said study co-author Joseph Wall, a biophysicist at the U.S. Department of Energy's Brookhaven National Laboratory.

Previous studies of the type III secretion system have shown that it is composed of some 25 different kinds of proteins assembled into three major parts: a "bulb" that lies within the bacterial cell, a region spanning the inner and outer bacterial membranes, and a hollow, largely extracellular "needle." Using a combination of scanning transmission electron microscopy and transmission electron microscopy, the scientists have now revealed new details of the "needle complex" structure.

The more accurate model therefore shows how the different parts of the injection machine fit together and may fit with other bacterial components that provide the engine to drive injection. These are important steps toward developing a detailed understanding of how the injection machine works, and to developing inhibitors that can prevent bacterial infections.

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