Cholera’s Spring Loaded Nano-dagger

Bacteria have a number of tools to fend off foes or attack competitors, but now a new method can be added to the list: a spring-loaded dagger

Research published in Nature by scientists at the Harvard Medical School and the California Institute of Technology investigated the structure of a mechanism used by the bacteria vibrio cholera to kill both competing bacteria and human cells, called the Type VI Secretary System (T6SS) in the cholera bacterium.

Scanning electron microscope image of Vibrio cholerae bacteria, which infect the digestive system

It’s known that T6SS can deliver toxic proteins into nearby cells, but until now the exact mechanism was not known; now it appears T6SS could be using a poison tipped dagger to deliver this killing blow.

“People aren’t surprised that animals have really interesting ways to hurt each other – snakes have venom, bears have claws,” says Grant Jensen, professor of biology at Caltech and co-leader of the study. “But they might be surprised that a single cell within one of those animals’ bodies is still 100 times larger than the bacterial cells we’re talking about, and yet the bacterial cells contain weapons that are so sophisticated. That’s the marvel.”

Using a fluorescent label attached to a protein called VipA, known to be involved in T6SS, the researchers were able to watch nano-meter sized tube like structures grow in real-time. The structures attach to a ‘base plate’ on the cell wall and grow over tens of seconds, then contract in milliseconds. Up to six tubes could be seen growing in each cell at any one time.

The researchers suggest the tube develops like an elastic sheath around a smaller tube, the ‘dagger’, which could be tipped with a toxic payload. Following an unknown signal the outer sheath suddenly contracts and fires the ‘dagger’ out through the cell wall, and, possibly, straight in to its target. The sheath then disassembles and is rebuilt elsewhere ready to fire again.

The researchers also used a technique called ‘electron cryomicroscopy’, where samples are quickly frozen in water and examined at super high magnification under an electron microscope, to examine the structures in the bacteria.

“When the tube contracts, that’s when it shoots,” says Martin Pilhofer, a postdoctoral scholar in Jensen’s lab. “That result agrees well with what we had seen using the electron cryomicroscope, where we observed long tubular structures in two different conformations—extended and contracted. Whereas electron cryomicroscopy allowed us to observe the secretion apparatus at high resolution, the fluorescence study gave us more insight into the dynamics of the system.”

Understanding how T6SS works could be used to develop drugs that target the toxin delivery system and so help treat infections like cholera, or to engineer bacteria to use T6SS for our own purposes.

“Someday, we’d like to be able to re-engineer and repurpose T6SS systems to perform tasks of our choosing,” said Jensen. “For instance, inserting toxins into cancer cells.”

Disclaimer: Assuming you made it this far, this was written as part of a portfolio to submit for my MSc (as a ~300-500 word news story). This was aimed as being an online piece for the Guardian.

I had to use quotes (only quotes) directly from the university press releases, which I don’t really like doing, so feel a little dirty, but I hope you don’t mind.

Update: Just found their video, which is great.