Bacteria can share vital nutrients if their bacterial neighbors happen to have a surplus. Scientists have now determined that this sharing is accomplished not through diffusion of those nutrients into the surrounding environment, but rather via nanotubes that physically link the insides of two bacterial cells together.

Photo Credit: Michael B. Keller/US Air Force. CC BY-NC 2.0.

Bacteria are often cooperative symbionts (players in a symbiotic relationship), in spite of their popular notoriety as pathogens. This probably isn't news to you if you've followed recent stories about fecal transplants curing gut diseases by shifting the balance of bacterial strains in the gut, or female mice passing their traits to their offspring via bacteria, instead of their own genes.

Symbiosis is, by definition, a give-and-take. We've known for quite some time that bacteria are master traders of various forms of cellular currency: genetic code (DNA and RNA), proteins, nutrients, and even antibiotics. But because bacteria are so small, and so diverse, the details of this give-and-take are usually studied one at a time, in the artificial environment of the laboratory.

Just over a year ago, the lab of Christian Kost, based out of the Max Planck Institute for Chemical Ecology in Jena, Germany, showed that two strains of bacteria, genetically engineered to lack one nutrient and overproduce another, could support one another in the same flask if their deficiencies and surpluses were complementary. On their own, either strain would not survive. (The nutrients were the two amino acids, histidine and tryptophan).

In fact, these 'dependent' bacterial strains grew 20% faster than if they hadn't been engineered to require an external source of a particular amino acid. This result suggested that this type of symbiosis was not only possible but beneficial, perhaps explaining the overwhelming prevalence of bacterial symbiosis in the natural world.

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But how were these single-celled bacteria actually trading these nutrients? Were they simply pumping out their own specialty amino acid, while desperately gobbling up any free amino acids produced by their bacterial sidekicks? Or was the trade more personal, somehow? In the past, researchers have observed directly neighboring cells engaged in nanotube-mediated DNA transfer. Was the same thing happening here, with amino acids?

The Kost lab grew up their various types of bacteria in a liquid broth, and then placed complementary strains on opposite sides of a fine filter within the same flask. This filter would allow both types of amino acid to freely flow between the two sides of the flask – however, it would prevent the histidine-deficient/tryptophan-producing bacteria from physically touching their histidine-producing/tryptophan-deficient counterparts.

Deprived of physical interaction, the strains somehow lost their ability to trade amino acids, and both bacterial communities died. The scientists returned to their original, living co-culture of complementary strains, and zoomed in with an electron microscope to figure out what type of physical interaction was responsible for amino acid trade.

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Remarkably, the bacteria had managed to physically connect themselves with one another using microscopic tubes (nanotubes). This network of nanotubes facilitated a vital trade of histidine and tryptophan that was allowing both strains to thrive.

Electron microscopy image of E. coli using nanotubes to survive off of a continuous trade of amino acids with other bacteria. Martin Westermann, University Hospital of the University of Jena.

One big questioned remained, though: could symbiosis still be achieved using different bacterial species for the complementary strains, or did both strains need to match?

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Surprisingly, the nanotube network only emerged when both strains were derived from E. coli (a familiar gut microbe), or when one strain was E. coli, and the other strain was derived from the soil bacterium, Acinetobacter baylyi. E. coli was a required partner for amino acid trade to occur, a boon for A. baylyi, which was incapable of forming nanotubes on its own.

Luckily, this species-dependency of the experiment provided the researchers with a necessary clue for determining how the nanotubes were forming, as Kost described in a press release:

The major difference between both species is certainly that E. coli is able to actively move in liquid media, whereas A. baylyi is immotile. It may thus be possible that swimming is required for E. coli to find suitable partners and connect to them via nanotubes.

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E. coli seemed to be capable of adapting some of its motion machinery for seeking out, and then hooking up with, any bacteria that could compensate for its nutritional deficiency. E. coli could also sense whether such nanotubes were necessary for survival. If the scientists supplied the missing amino acid directly, in the culture broth, E. coli would refrain from extending out these nanotubes in the first place.

Moreover, the work showed that symbiosis within bacterial communities might have a more physical underpinning than once assumed. This bacterial symbiosis somewhat resembles simple forms of multicellular life, like sea sponges, or certain types of fungi, which are composed of numerous identical cells that have figured out how to physically stick together.

"To me, the most exciting question that remains to be answered is whether bacteria are in fact unicellular and relatively simply structured organisms or whether we are actually looking at some other type of multicellularity, in which bacteria increase their complexity by attaching to each other and combining their biochemical abilities," Kost summarized.

It's certainly not time to trumpet bacterial multicellularity, but bacteria are clearly wiser than we often given them credit for.

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Read the full scientific study in Nature Communications.