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Sabotaging bacteria to halt infections

Motile bacteria move through the function of flagella. These appendages rotate, which propels an organism forwards. This is a little like the propellers on a boat. Some bacteria have one flagellum, others have many, and some possess none at all. Some of the bacteria regarded as human pathogens have flagella. An example of a flagellate bacterium is the ulcer-causing Helicobacter pylori, which uses multiple flagella to propel itself through the mucus lining to reach the stomach epithelium. Some flagella also serve a function in environmental detection, sensing different conditions and signalling to a bacterium to move to or away from a given niche.

The idea of disabling flagella to prevent bacterial movement has come from Dr. Hideyuki Matsunami of the Trans-Membrane Trafficking Unit at the Okinawa Institute of Science and Technology Graduate University (OIST).

The new research puts forward the idea that one way to disrupt the flagella is to alter their development. Given that all the proteins that make up the visible part of flagella are synthesized inside the bacterium, and there are then subsequently secreted through a channel through the bacterium’s membranes, this is a suitable point to disrupt the process.

This has led to work on a protein seen as critical to the development of a flagellum. The identified protein exists in two different geometric forms. When the protein is rendered ‘narrower’ in shape the flagellum cannot exit the bacterial cell. This means the organism is no longer motile.

The protein shape can be altered through the use of a small molecule and early experiments show this to be effective. What is limiting process is the application: the modification needs to take place outside of the bacterial cell, whereas a more effective method would involve using a chemical cocktail that can be absorbed by the bacterium. This remains part of work going forwards. A further factor to resolve is the differences between bacterial species and the variations between species. Work to date has been with a species of Salmonella bacteria.

Discussing the concept further, from Dr. Matsunami told Controlled Environments magazine: “When you have a bacterial infection, the first action is to take antibiotics.” However, since antibiotics may not be effective, or carry side-effects, alternatives have been considered. This has led to new “thinking about is how we can disrupt infections, but without just killing any bacterium. One way to do that would be to disrupt the bacteria’s motility, which means to disrupt the flagella.”

The research findings are published in the journal Scientific Reports. The research paper is titled “Structural flexibility of the periplasmic protein, FlgA, regulates flagellar P-ring assembly in Salmonella enterica.”

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Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, business, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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