Some bacteria are known to inject toxins into host cells using a syringe-like appendage. Past research has found that we might be able to hijack that as a new drug delivery system, and now scientists from the Max Planck Institute have developed a way to control the mechanism using light.
The appendage is known as a type three secretion system (T3SS), and it’s used by certain strains of bacteria like E. coli, Salmonella, Shigella, Yersinia (the family that causes the plague), and Pseudomonas, which is responsible for many hospital infections.
The nasty little critters latch onto a host cell, and push several thousand unpleasant proteins into the cell through the T3SS. These can suppress the host’s defenses and help the infection spread, as well as contributing to symptoms like fever, diarrhea and pain.
Nefarious as it is, this injection system is undeniably effective. So of course, scientists are trying to take advantage of it for more helpful purposes. Just a few months ago, the Max Planck team reported that they’d managed to hijack the T3SS to inject useful chemicals like drugs into cells instead.
But there remained a problem: the system isn’t very precise. It doesn’t discriminate which cells it injects, instead just launching its payload into whatever cell the bacteria happens to bump into.
“As soon as a T3SS contacts any host cell, it fires its load immediately,” says Andreas Diepold, lead researcher on the study. “This is unfavorable for applications in biotechnology or medicine, where we want to target specific cell types, for example in tumor therapy.”
The key to that control is light. Optogenetics is an emerging field where pulses of light at specific wavelengths can be used to influence certain molecular processes. In this case, the researchers hooked up an optogenetic switch to a dynamic component of the T3SS. The injection system could then be switched on and off with pulses of blue light.
They called the resulting system LITESEC-T3SS. In lab tests, the team used the new technique to inject fluorescent proteins into cancer cells, causing them to glow blue. While that was a demonstration to check that the mechanism worked, in another test the team swapped the payload protein for one that induces cell death, and set it loose on cancer cells. Sure enough, it was effective at killing the tumors.
The researchers plan to continue experimenting with this technique to see what else it may be capable of. There’s still plenty of work left before it could ever become a viable treatment.
The research was published in the journal Nature Communications.
Source: Max Planck Institute
