Small Talk - The Secret Conversations Of Bacteria

Can you remember the last sunny day you spent in a park? As you basked on the grass, you could probably hear conversations all around you: couples cooing, teenagers cackling, dogs barking at singing birds. But you probably weren t aware that close by in the soil, beneath pond water, on your very skin! billions of invisible bacteria were communicating in a secret code. We only became aware of this chatter a few decades ago, but since then our understanding has rapidly improved. Both disease-causing bacteria and friendly ones that benefit their hosts rely on communication. Now we are learning how this bacterial language works, and once we are fluent, we may be able to control the behaviour of microbes for our own benefit.

Like all good stories, ours begins with a glowing squid. March 1968. Otis Redding is sitting on the dock of the bay and at the top of the singles charts. Yuri Gagarin, the first human to travel into outer space, dies aged 34 in a supersonic plane crash. Protests rage against Communism in the Eastern Bloc, and the Vietnam War in America. In Texas, Ellis Kempner and Frank Hanson are puzzling over how a bacterium from the sea now known as Aliivibrio fischeri produces light.

This process, known as bioluminescence, is widespread throughout nature and can be used to attract mates, lure prey, and deter predators. The vast majority of light-emitting animals are found in the ocean while most produce their own light, some have specialised light organs which house glowing bacteria. This is a classic example of symbiosis, where two organisms cooperate to benefit each other: the bacteria pay rent on their comfortable home as light, which the animal uses to gain a competitive edge in the ocean. Aliivibrio fischeri, the bacterium Kempner and Hanson were interested in, has just such a relationship with the Hawaiian bobtail squid, a tiny two-inch-long creature found near the shore. It lives a nocturnal life, and as it swims near the surface, the moonlight shining on the waves gives it a telltale silhouette, making it easy pickings for hungry seals. However, the squid has evolved an effective defence mechanism: counterillumination. The bobtail squid allows A. fischeri to grow in its light organ, which is fitted with a sack to hold bacteria, two lenses, and a reflector. This setup is used to illuminate the squid s body to an appropriate level, depending on the strength of light from above, effectively eliminating its silhouette.

But A. fischeri can also be found living on decaying matter on the seafloor, and in this environment, it doesn t glow at all. Scientists also observed this phenomenon when they grew the bacteria in the lab: no light when the bacteria started growing, but as they divided and grew more numerous, they would begin generating light. The magic number that caused this switch in behaviour was around two billion bacterial cells per millilitre of liquid culture. But the key observation that Kempner and Hanson made in 1968 was that you don t actually need to have that many bacteria present. If you grow A. fischeri to that magic number and then remove all of the bacteria from the liquid, you can grow a much smaller number of cells in this preconditioned broth and they will immediately begin glowing. How is this possible? The bacteria were leaving a message behind when they were removed, and this message instructed a smaller number of the same species to produce light. The bacteria were communicating!

It took twenty years for researchers to understand what this message was, and how it worked. Two key proteins are involved. LuxI makes the message, a simple molecule with a complicated name: N-(3-oxo-hexanoyl)-L-homoserine lactone, which moves freely in and out of the bacterium. More and more of this chemical signal accumulates in the environment as A. fisheri cells divide and increase in number until a critical concentration is reached. At this level, the molecule binds enough LuxR proteins in the bacteria to trigger a behavioural switch: LuxR activates the cellular machinery that produces light. In essence, LuxI does the talking and LuxR the listening . This simple system ties light production to the number of A. fisheri cells that are present. That relationship is critical because the light produced by a few bacteria is too weak to bother wasting energy on it s only worthwhile to shine when enough cells nearby are also shining. This form of communication is called quorum sensing: the microbes tell each other about their numbers and perform a behaviour together when the minimum amount of them required a quorum is present.

But there s more to this process. Activated LuxR also causes more of itself and LuxI to be made, intensifying the signal in what s known as a positive feedback loop . Imagine a herd of buffalo being stalked by lions. A few individuals spot their predators and are startled into running. This increases the level of panic in the group, encouraging more buffalo to run, which in turn spreads more panic until you have a stampede. Similarly, once a quorum sensing system is activated in a few bacteria, communication gets louder and louder until the entire group performs a behaviour as one.

Over the following years, scientists discovered the genes for quorum sensing in many species of bacteria. The details the structure of the chemical signal and the behaviours controlled vary, allowing a species to have private conversations. The basic mechanism, however, is the same. A bacterial protein makes a signal, the signal builds up as the number of bacteria increase, and another protein senses the signal and activates a behaviour when enough bacteria are present. Quorum sensing has been shown to control the production of toxins, the exchange of DNA, and the formation of hardy spores to survive starvation.

Importantly for us, quorum sensing is also involved in bacterial infections. Pseudomonas aeruginosa is a wily bacterium found in soil and stagnant water. The microbe has a whole utility belt of tricks that allow it to infect plants, insects, and humans when the opportunity arises. It targets the vulnerable: intensive care patients, burn victims, and those with weakened immune systems, including premature babies. An infection can cause pneumonia or even eat away at bowel tissue, which kills one in four of those affected. Worryingly, cases are on the rise, and P. aeruginosa is learning to beat antibiotics, making it much harder to treat.

To establish an infection, the bug must produce a cocktail of toxins, destructive enzymes, and molecules that scavenge nutrients. This requires a lot of energy, so it only makes sense to turn on production when enough bacteria are present to have an effect. Therefore, quorum sensing plays a key role in infection. This presents an opportunity: if we can find a way to interfere with this signalling in P. aeruginosa if we can jam their comms we should be able to stop infections. Molecules have been discovered that can interfere with quorum sensing and clear P. aeruginosa from the lungs of infected mice, and the hope is that these can be developed into drugs for the clinic.

Anything that relies on cooperation is vulnerable to freeloaders: those who cheat the system by benefiting from a public good without paying in. If you ve ever worked in an office you ll be familiar with this situation. Most breakrooms have a coffee maker. Colleagues must refill the pot when it s empty, and although this requires time and effort from an individual to make more coffee than they need, as long as everyone pitches in there is plenty to go around. However, if enough people never contribute, the system fails: there s never any coffee when you want it, and a few people are exploited. Bacteria also cheat. They can mutate so that their quorum sensing system no longer functions and benefit from the work their relatives do without contributing. Here is another opportunity to tackle infections it may be possible to infiltrate groups of infectious bacteria with cheats that reduce the fitness of the group until they all die. There are also bacteria that eavesdrop on the chatter between other species. Pseudomonas aurefaciens produces antibiotics when it detects quorum sensing molecules, killing competitors as they appear. Ingeniously, Variovorax paradoxus can use quorum sensing molecules as its only food source, preventing other species from talking and getting a free lunch in one fell swoop.

As our understanding of bacterial communication improves, we can attempt to speak the language. Synthetic biologists aim to redesign living things to fulfil useful new functions. They have used quorum sensing to improve the production of biofuels by E. coli cells acting like miniature factories, offering a cost-effective route to a green energy source. The possibilities of speaking to bacteria are almost endless. So next time you have a quiet moment, spare a thought for the countless conversations going on unheard all around you.