Shut Up! Why Stopping Bacterial Conversations is Good for Your Health

The Language of Bacteria

Think back to the last time you planned to do something with your friends. There was a fair amount of talking involved, right? It is the same for bacteria (although, they are less concerned with what movie to see or where to eat and more interested in invading and colonising a suitable host). Bacteria have developed a highly effective method of communication known as quorum sensing. While quorum sensing is exceptionally useful for bacteria, it isn’t a simple process.

Bacteria communicate using molecules known as autoinducers. However, not all bacteria can understand each other’s signals. Image by Chris Proctor — *Bacteria communicate using molecules known as autoinducers. However, not all bacteria can understand each other’s signals.*
*Image by Chris Proctor*

Quorum sensing depends on the number of bacteria present at any given time. Each bacterium constantly produces, and releases chemical messages called autoinducers, which build up in the cells’ immediate environment. These autoinducers vary in size and shape depending on the bacteria that produces it. Just like languages that are specific to the part of the world we come from, the set of autoinducers produced is also specific to the bacterial species producing them. The unique nature of these autoinducers means that bacteria can only communicate with bacteria of the same species. However, this is not always the case. Some bacterial species are “bilingual” meaning that they can produce autoinducers that can be detected by several other species.

What do Bacteria Talk About?

Once enough bacterial cells are present and producing a high enough level of autoinducer, the bacteria respond to the message and start to work as a team. Together, they coordinate the production of different molecules and even coordinate how the cells move. This teamwork is what ultimately allows bacteria to survive in various environments.

Even though quorum sensing is beneficial for bacteria, it can often be very bad for our health. By using quorum sensing, bacteria are able to cooperate to efficiently infect a host and make their new home more tolerable. They achieve this in several ways.

Firstly, bacteria use quorum sensing to produce molecules, known as virulence factors, which are beneficial to them. A good example of this comes from a common and infamous bacterium, Staphylococcus aureus. When enough of these bacteria colonise a human host, they coordinate the production of a molecule called hemolysin. This molecule helps the bacteria to acquire essential nutrients and compounds important for their survival.

Sounds harmless, right? Unfortunately, they do this by bursting (or lysing) our red blood cells allowing the bacteria to take up and use the nutrients inside. Sometimes, this blood cell destruction is not widespread enough to be particularly problematic for the host. However, in other cases, hemolysins can cause severe damage in lung tissue during diseases like pneumonia.

By stopping them from easily communicating with each other, we may be able to make some bacteria less harmful to humans.  Image by Chris Proctor — *By stopping them from easily communicating with each other, we may be able to make some bacteria less harmful to humans. Image by Chris Proctor*

Another example is the bacterium Pseudomonas aeruginosa which produces a molecule called pyocyanin. Pyocyanin is used by Pseudomonas to ward off other bacterial species which may be trying to compete with them for space and nutrients.

However, in humans, when pyocyanin is present in lung infections it can cause prolonged inflammation leading to tissue damage. P. aeruginosa also produces compounds such as exotoxin A, which can cause human cells to die. This cell death is particularly problematic in infected wounds as dead tissue can worsen the wound. This delays its healing and increases the likelihood of developing further complications.

As well as helping in the production of harmful virulence factors, quorum sensing can also enable the formation of biofilms, which are not always good for your health. Biofilms are like bacterial fortresses; they are made up of large numbers of bacteria held inside a tough but gooey scaffolding. Biofilms protect bacteria from being attacked by our immune system or killed by antibiotics. They also provide an ideal environment for bacteria to become stronger and more resilient to antibiotics by sharing useful genes among their population.

Importantly, the formation of biofilms is almost entirely coordinated by quorum sensing. In addition to providing extra protection these biofilms harbour bacterial persister cells. These cells are like sleeper agents and lay dormant for long periods of time and can even survive treatment with antibiotics. These cells can later become activated and establish a new infection and build new biofilms and continue making us sick.

How do we shut them up?

As you can see, quorum sensing is essential for bacterial function and survival. This means that if we impair communications, bacteria will be out of sync with one another. Many scientists have discovered what we call quorum sensing inhibitors (QSIs) that block bacterial communications. These QSIs work in several ways including breaking down the signalling molecules or blocking the bacteria’s ability to detect them entirely. Interestingly, many QSIs can be found in our kitchen cupboards!

Not only does cinnamon taste great but it may also be the next weapon in the fight against bacteria. Specifically, one of cinnamon's primary flavour and aroma compounds, cinnamaldehyde, has been shown to reduce the production of harmful molecules produced by bacteria through quorum sensing. As well as cinnamaldehyde, several other store cupboard ingredients have been shown to have anti-quorum sensing action and have even been seen to reduce the production of virulence factors and interfere with biofilm formation.

Clove oil has also been shown to stop bacteria in their tracks. By interrupting the communication between cells, clove oil can reduce the movement of Pseudomonas bacteria. This will prevent bacteria from effectively forming a biofilm to further protect themselves.

Also in the anti-quorum sensing spice rack is vanilla. Just like cinnamon and clove it can effectively reduce the ability of the bacteria to receive and detect the autoinducer signalling molecules.

It’s not just spices that contain anti-quorum sensing molecules. A wide range of fruits and vegetables have compounds that can achieve this as well. These compounds include limonene (from citrus fruits), furanones from (seaweeds, strawberries, pineapple and many others) and some sulphur containing compounds from vegetables such as broccoli.

While it is great that all these compounds can be found easily and can inhibit bacterial talk, making the bacteria less dangerous, there is another reason they are so promising. Antibiotic resistance has been a growing concern for many years and with the emergence of new pan-resistant bacteria (bacteria resistant to all routinely used antibiotics) efforts to develop new treatments have increased.

However, bacteria are highly resourceful, and it doesn’t take them long to develop resistance to new antibiotics. This is where quorum sensing inhibitors could become important. Not only can they make bacteria less dangerous and more treatable, but they can do this at concentrations that do not kill the bacteria. This means that the bacteria have no reason to develop resistance against them. If this is the case, molecules such as these could be used alongside traditional antibiotics to treat previously resistant infections.

So, what next?

By preventing communication using QSIs we can make life very difficult for many bacteria while potentially improving treatments for infections and addressing antimicrobial resistance. Image by Chris Proctor

It is clear that quorum sensing inhibitors are promising compounds. But how can they be used to treat patients? Unfortunately, it’s not as easy as making yourself a fruit cake, full of cinnamon, clove and vanilla. The compounds often have to be applied directly to the bacteria and this makes using them more difficult. Due to a lack of research involving anything more complex than a mouse, or even some cells in a dish, we can’t be certain how these compounds will affect humans if used in high enough concentrations to inhibit quorum sensing.

However, if they are found to be safe, quorum sensing inhibitors could have numerous applications. One of the main potential uses would be as a supportive treatment to be administered alongside currently used medications. This could take the form of a dose of inhaled quorum sensing inhibitor to be taken along with antibiotics to help clear chronic chest infection in patents with conditions such as cystic fibrosis.

Alternatively, quorum sensing inhibitors could be used as a coating on medical implants and devices. For example, a urinary catheter coated with the correct compound would be less susceptible to acquiring bacterial biofilms which can lead to urinary infections and even sepsis. These applications only scratch the surface of the potential applications for quorum sensing inhibitors.

Bacteria are always talking to each other and that’s not always good for our health. With on-going research into the various compounds that can interrupt this chatter we are edging closer and closer to effective methods and treatment that can tell pathogenic bacteria to shut up.