Healthcare breakthrough turns bacteria into cyborgs and drug factories

For some time now many experts have believed that one of the ways we can, possibly, conquer disease is by simply turning bad bacteria “off,” after all, if you can turn a bad bacteria off then you can either stop the disease in its tracks, or minimise its impact.

Now, in a world first, researchers from the University of Maryland (UM) have taken a giant step forward and created what they’re calling an “Electrogenetic Switching System” (ESS) that they’ve been able to use to turn parts – albeit not whole bacteria yet – on or off, and as a consequence they’re able to influence how the single celled organisms behave.

Cells respond, and send signals and instructions to other cells, via molecular signals using a process called Gene Expression where the information stored in each cell’s DNA is converted into instructions, each of which represent a different action, by creating molecules such as proteins, enzymes and hormones.

Microelectronic systems, like the ones that the team from UM used to build the new molecule scale on-off switch, by contrast, communicates via electrons, which are usually generated by an energy source.

Although there's no way electrons can flow freely within a biological system like electricity does through a wire, there’s a small class of molecules, called “Redox” molecules, in most cells that can stably shuttle electrons that can "hand off" electrons when they undergo Reduction or Oxidation reactions. Redox reactions are chemistry 101 so you might be familiar with them from high school.

With minimal rewiring, the team was able to modify these redox molecules to respond to electrons from the electrode of a patent pending microelectronic device that could toggle the molecule's oxidation state into either an oxidised state, where it would lose an electron, or a reduced state where it would gain an electron. Essentially turning the redox molecules on and off.

The team were then able to manipulate the bacteria to respond to the redox molecules on-off state by activating specific gene expressions which created the ESS that could turn parts of the bacteria on or off at will when a voltage was applied.

In one example, the researchers were able to engineer a bacterial cell to turn the cell on so it would synthesize a protein that emits a fluorescent green hue, and off so it would stop synthesising the protein. The cell would literally light up when it was switched on.

In another example, they applied the method to bacteria that express a protein called CheZ that controls its swimming activity. The scientists could turn the part of the cell that synthesized Chez on and off, controlling whether the bacteria moved forward or not.

They also applied the method to bacterial cells that contain a natural biological signalling molecule that is used to communicate with neighbouring cells which caused changes in the collective behaviour of a whole community of bacteria.

The ESS device also let the researchers electronically program the group to repeatedly cycle a programmed behaviour.

The new research ties into the teams previous work where they found ways to "record" biological information by sensing the biological environment, then, based on the information, write electrons to small electrochemical devices that recorded it.

Using these electrochemical devices, the team were able to identify pathogens, and even monitor signs of stress in the blood levels of people with Schizophrenia. As a consequence, if these two research streams are combined we could one day be able to electronically program bacteria to deliver drugs to a specific sites in the body to help alleviate the symptoms of disease and syndromes.

"For example, imagine swallowing a small microelectronic capsule that could record the presence of a pathogen in your gut and that also contained living bacterial factories that could manufacture the right anti-microbial or other therapy – all in a programmable autonomous system," said William Bentley who led the research.

"Electronics have transformed the way we live our lives, and there have been increasing efforts to 'connect' devices to biology, such as glucometers and fitness trackers that use sensors to access biological information," added Gregory Payne, who was a member on the team, "but, there are far fewer examples of electronics communicating in the other direction to provide the cues that guide biological responses. Such capabilities could offer the potential to apply devices to better fight diseases such as cancer and help promote wound healing."

The results of the research have been published in the journal Nature.