Medical

Hijacking bacteria's lethal injections allows nano-syringes for drugs

Hijacking bacteria's lethal in...
An artist's rendition of bacterial nano-syringes, injecting toxins into host cells
An artist's rendition of bacterial nano-syringes, injecting toxins into host cells
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An artist's rendition of bacterial nano-syringes, injecting toxins into host cells
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An artist's rendition of bacterial nano-syringes, injecting toxins into host cells
How the bacterial nano-syringe injects toxins into cells
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How the bacterial nano-syringe injects toxins into cells

While there are many that are good for us, bacteria can be insidious little organisms, with some of them using tiny syringes to inject toxins into their host’s cells. Now, researchers from the Max Planck Institute have found a way to use this to our advantage, by swapping out these toxins for other chemicals, like drugs.

Many bacteria infect their host’s cells using this syringe mechanism, including E. coli and Yersinia – the bacterial family that causes the Plague. These bugs latch onto a cell, then push a channel through its protective membrane. From there, the bacteria passes a toxic protein into the vulnerable center of the cell, usually killing it within minutes.

The researchers at Max Planck had previously studied this process using cryo-electron microscopy. As the name suggests, this involves chilling samples to cryogenic temperatures, then examining them through powerful electron microscopes. That allows the scientists to see the structure of these proteins in three dimensions and high resolution.

For the new study, the team investigated whether they could switch out these toxic protein payloads for something a bit more beneficial. And sure enough, they could – provided three criteria were met.

First, the protein has to be a certain size – larger than 20 kiloDaltons (kDa), for those of you playing at home – in order to remain stable. Secondly, they have to be positively charged. And thirdly, they can’t interact with the molecules that form the “capsule” that holds the payload.

How the bacterial nano-syringe injects toxins into cells
How the bacterial nano-syringe injects toxins into cells

“With this technique, we have taken the first step towards our ultimate goal of using these nano-syringes in medicine to introduce drugs into body cells in a targeted manner,” says Stefan Raunser, lead researcher on the study.

While the process may be adapted to deliver good drugs to cells, in some cases it could also still be handy to inject toxic proteins as well. The team says that nano-syringes could be designed to sniff out cancer cells, latch on and deliver poisons to them, without harming healthy cells. But in order for that to work, more research needs to be done to determine how the molecules connect to the cell surface.

“We are currently looking for the toxin's ‘docking stations’,” says Raunser. “Once we have found them and understood how the toxin binds to the cell surface, we aim to specifically modify the injection mechanism so that it can recognize cancer cells. We could then inject a killer protein exclusively into tumor cells. This would open up completely new possibilities in cancer medicine with minimal side effects.”

The study was published in the journal Nature Communications.

Source: Max Planck Institute

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