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Making bacterial syringes
Neil Baugh
April 24, 2024
TLDR: Scientists hijack a bacterial injection system to better deliver protein drugs
Turns out it’s tough to deliver protein therapies in an effective way. We don’t have many good delivery systems for proteins and it’s an active area of research (and what I’m currently doing my PhD on). Today’s post looks at a new and innovative way to take advantage of natural protein delivery methods.
Bacterial Syringe schematic. Kreitz et al. Nature. 2023
Big Takeaways
Bacteria use syringe-like injection systems to deliver proteins into cells.
The syringes recognize a specific cell type, drive a spike through the cell membrane, then release their protein cargo.
Scientists modified the syringes to load desired protein drugs and recognize human cells.
Hijacked bacterial syringes are highly specific and efficient delivery systems for a leukemia therapy.
The Problem
You have about 100 trillion bacteria living in your digestive system right now that help you break down food, stay healthy, and even communicate with your brain. In fact, you have around 10x more bacterial cells in your body than human cells.
Sometimes all bacteria want to do is live in peace with their host. However, to do this they occasionally need to be a bit aggressive. They often release proteins that let the host (aka you) tolerate their presence.
It’s not enough to just create some proteins. The bacteria have to get these proteins inside of the host cells for them to work. And the proteins don’t go in by themselves.
Some bacteria use a “contractile injection system” to get proteins inside their targets. These are nano-sized little syringes that load up a protein inside of them and then literally inject it into the target. See the image at the top and it’ll make sense. Plus they look like moon landers.
TEM image of bacterial syringes. Arrow points out a “contracted” syringe. Scale bar 100nm. Kreitz et al. Nature. 2023.
The Solution
This week’s scientists figured out how to hijack the contractile injection system and turn it into a versatile tool for delivering protein drugs as a new type of cancer therapy.
The authors instructed bacteria to produce empty syringes and figured out how to purify them. Next, they used another recent finding to load proteins of their choice into the syringes.
The ends of tail fibers are responsible for targeting specific cell types. Kreitz et al. Nature. 2023
They found that certain regions on the tails of the syringes were responsible for targeting specific cell types (the “Tail Fibers” in the schematic above). Parts of these tail fibers could be switched out to make the syringes act on the desired cells, like cancers.
As an example, they modified their syringes to target leukemia cells and loaded them with toxins. This cancer-targeting and toxin-loading led to the syringes killing nearly all of the cancer cells without killing other non-leukemia cells (see graph below).
Bacterial syringe modified to kill Leukemia cells but not healthy cells. Kreitz et al. Nature. 2023
Some of the most powerful drugs we have come straight from nature. We might as well deliver them with bio-inspired technology too.
See you next week for more science,
Neil
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