ABOVE: Microbial communities deep beneath the surface of the earth could contain new strains of electrochemically active bacteria. Yamini Jangir

While humans and (nearly) every other animal on the planet require oxygen to survive, many species of bacteria have gotten a bit more creative.1 Instead of using oxygen as the final electron acceptor for cellular respiration, some bacteria can use iron or manganese, effectively “breathing” metal.2 From the initial discoveries of Shewanella oneidensis and Geobacter metallireducens in the sediments of Oneida Lake and the Potomac River, these “electric bacteria” have risen to stardom as components of microbial fuel cells and microbial electrosynthesis for the production of fuels and other biochemicals.3–6

Moh El-Naggar, a biophysicist at the University of Southern California (USC), has been fascinated by these organisms for nearly two decades. After years of studying the dynamics of electron transfer in these bacteria individually and in biofilms, El-Naggar is exploring how these organisms could provide an interface between the living and nonliving worlds, using the expertise developed by evolution to create hybrid electronics.

How did you get into the field of electromicrobiology?

As a graduate student at the California Institute of Technology, my training was in applied physics and materials science. When I was wrapping up my graduate studies in 2006, I was interested in moving into the biophysics world. I had this idea in my head that instead of joining a physics lab that does biology, the best option would be to join a biology lab—to plunge in and just see how it worked.

We just discover something, and then there are enough smart people in the world to take it in unexpected directions. It’s one of the biggest arguments for basic research.
-Moh El-Naggar, University of Southern California

That meant that I was looking for postdoctoral job openings that I was utterly unqualified to fill. I had never even streaked a plate to grow bacteria before. During those days, I contacted a bunch of people, and one day, I called Ken Nealson, a really distinguished microbiologist at USC. I only later found out that he was the scientist who first isolated Shewanella oneidensis, which became a model organism for studying this new class of microbes that we now colloquially call electric bacteria.3 

I said, “I heard that you're doing all these interesting projects with bacteria and electrons. I might know something about electron transfer, but I've never worked in bacteria.” Instead of turning me down, he asked if I could drive down to USC that afternoon. It all worked out from there. So, my entry into the field was basically a cold call to a very distinguished microbiologist who decided to take a flyer on me.

How did the discovery of electric bacteria by Nealson and other researchers in the 1980s change how scientists understood cellular respiration? 

Before the late 1980s, people knew that there were anaerobic bacteria that didn’t need oxygen to survive. But the general wisdom was that whatever molecule the bacteria used instead of oxygen still had to be soluble; it still had to go inside the cells to be used in respiration. What Ken and another really distinguished microbiologist Derek Lovley at the University of Massachusetts Amherst independently discovered were anaerobic microbes that functioned differently. Instead of waiting for the electron-accepting molecule to go into the cell, the bacteria transport the electrons outside of the cell to a solid surface.

Why would this respiration strategy have evolved? In nature, there are lots of iron and manganese minerals that are redox active, meaning that we can give an electron to them. It’s just that these minerals can’t go inside the cell, so the bacteria have to extend their electron transport chains to the abiotic world around them. 

How are the bacteria able to export these electrons?

Blue and yellow rectangular cable bacteria form long filaments.
Cable bacteria are multicellular bacteria capable of performing long-distance electron transport. 
Tingting Yang, University of Southern California

For a while, we have understood that electrons can move around in cells via electron tunneling: moving across very small distances, perhaps a few nanometers, between one molecule and another. It turns out that many of the organisms that we’ve been studying build these molecules called multiheme cytochromes that are essentially proteins with iron centers. An electron can hop from one iron to the next iron using this tunneling process.

One of our major contributions to this field was demonstrating that this process is not limited to single step jumps across a couple of nanometers; long chains of these iron-centred proteins can string next to each other. In this way, the electron can move not just a couple of nanometers, but up to many microns. In fact, it can travel even greater distances. Electrons can move through multicellular communities in the same way, from cell to cell to cell in bacterial biofilms. 

How has this research moved from basic science into exploring potential applications?

It's a cool science story because it went in such unexpected directions. At the beginning, researchers were excited about it because it was a new way of doing respiration, and they wanted to study the basic physiology. 

Then eventually researchers realized that if bacteria can send their electrons to surfaces outside the cell, we might be able to use them to build bio batteries. Instead of giving them a mineral, can we give them an electrode that looks like the terminal of a battery or a fuel cell? The answer turned out to be yes. After that, they began to wonder if the electron always has to go from inside the cell to the outside, or if this could be reversed. Instead of making electricity from bacteria, can we inject electricity into cells and have them do interesting chemistry, like reducing carbon dioxide to make fuels? 

We always like to think that we're so smart—that if someone discovers something that we'll know immediately what it's going to lead to. It turns out that the vast majority of the time, this is not the way it works. We just discover something, and then there are enough smart people in the world to take it in unexpected directions. It’s one of the biggest arguments for basic research. 

Where do you see this field going in the future?

In the last few years, I have been thinking about a class of devices that I refer to as living electronics. The idea is this: traditional electronics are very good, but there are things that biology is better at. For example, biology is very low energy; the power budget of running a whole bacterium is something that we just can't beat. To run an entire human being requires less power than an old-school incandescent light bulb. Even with this very low power budget, living things are very good at information processing and decision making. Cells are also very good at sensing; they can detect just a few molecules of something. 

Now, can we take these things that biology is very good at and couple this biology to traditional electronics that we know how to manipulate and handle? The key to putting these two pieces together is to have organisms where it is possible to communicate with them via electrons—and that's exactly what these microbes have naturally evolved to do. 

We know that bacteria can be used as biosensors, but what if I don’t just want a bacterium to express some green fluorescent protein when it sees the molecule I want to detect? Instead, I want it to send an electric pulse directly to traditional electronics. Similarly, can we use this for computing? Can I tap into the mechanics of how cells make decisions and provide input and output via an electric pulse? 

We've been studying how these bugs work, and we've been learning how to manipulate them on surfaces in a way similar to traditional electronics. Traditional electronics use lithography in order to pattern electronics in precise ways, and it turns out that we can use synthetic biology to pattern cells using light in a similar way.7 

Using optogenetics, we can create bacteria that increase or decrease the expression of the electron transport molecules in response to light.8 This is similar to semiconductor doping in traditional electronics; it’s increasing or decreasing electron transfer. This could enable us to start building things that look like transistors out of these cells. We'd like to play with the concept of coupling living cells to traditional electronics by taking advantage of something that certain bacteria have known how to do for a couple of billion years.

This interview has been condensed and edited for clarity.

References

  1. Yahalomi D, et al. A cnidarian parasite of salmon (Myxozoa: Henneguya) lacks a mitochondrial genome. Proc Natl Acad Sci U S A. 2020;117(10):5358-5363.
  2. Nealson KH, Myers CR. Microbial reduction of manganese and iron: new approaches to carbon cycling. Appl Environ Microbiol. 1992;58(2):439-443.
  3. Myers CR, Nealson KH. Bacterial manganese reduction and growth with manganese oxide as the sole electron acceptor. Science. 1988;240(4857):1319-1321.
  4. Lovley DR, et al. Anaerobic production of magnetite by a dissimilatory iron-reducing microorganism. Nature. 1987;330(6145):252-254.
  5. Cao B, et al. Silver nanoparticles boost charge-extraction efficiency in Shewanella microbial fuel cells. Science. 2021;373(6561):1336-1340.
  6. Rabaey K, Rozendal RA. Microbial electrosynthesis - revisiting the electrical route for microbial production. Nat Rev Microbiol. 2010;8(10):706-716.
  7. Zhao F, et al. Light-induced patterning of electroactive bacterial biofilms. ACS Synth Biol. 2022;11(7):2327-2338.
  8. Zhao F, et al. A red light-induced genetic system for control of extracellular electron transfer. bioRxiv. Published online January 1, 2023:2023.12.02.569691.