Cheatobiotics are one of the promising future treatments in patients presenting chonic infections. By reinfecting the patient with cheating bacteria that don’t contribute to the social cooperative effort in the biofilm it is possible to diminish the infection virulence in this chronic diseases, and make the biofilm more susceptible to antibiotics treatment.  Biofilms and quorum sensing understanding is key for the correct development of this cheatobiotics.

Bacteria are not lone wolfs. Biofilms

Even though bacteria can prosper just on their own, living in large communities of thousands of millions of individuals have its advantages. Everybody know bacteria don’t play with low numbers. But a community is not only about numbers. Creating a community is also about communication, relationship between individuals, and keeping some kind of organization. This is exactly what bacteria do when they grow in biofilms.

The “regular” bacteria, doing its bacteria things with joy in the mud, may not be alone there. But is surely enjoying its free will and movement liberty. They are living without knowing the planktonic “way of life”. A phenotype of the bacteria’s genotype. But, if proper conditions are given, it is believed that almos any kind of bacteria species can develop a biofilm. In this case, this little organisms will stick over a surface or to each other and, if the population is high enough, something very close to bacterial socialism will arose . Bacteria expressing this biofilm phenotype don’t only grow together sharing the space, but create a complex community within which the individuals share signals,  proteins, and structural or functional elements that they use in a collaborative effort. Everyone share and cooperate, and the addition of this collective small efforts is bigger than the efforts computed solely. Everyone…

This phenomenon is quite more frequent that you may think in fact. As you read this, the bacteria in your mouth are slowly but surely creating a biofilm over your teeth. So yes, dental plaque is one example of biofilm constituted by several species of bacteria. Embedded in a common matrix, they share extracellular DNA, polysaccharides, and proteins. Some of this bacteria generate acids as metabolites, like the lactic acid, that will eventually damage your dentin and produce a cavity.

Communication in biofilms. Quorum sensing

Before throwing yourself to a collaborative effort and the creation of the called “public goods” you may want to know that you are not alone. Fair enough. Communication is the key word here. And bacteria are small living bits that do so through chemistry. They constantly produce signalling molecules called autoinducers that the receptors in the cell membrane of any other bacteria can sense. When a high concentration of the specific molecule is perceived by the single individual, the conclusion comes readily: I’m not alone. In fact, when the autoinducers concentration reach a determined level, the bacteria perceiving the signal produce even greater quantities of the chemical, not only reinforcing and ensuring the communication, but providing an increasing relation between the population size and the autoinducer presence.

This mechanism is called quorum sensing, and it is key for the appropriate formation of these biofilms and modulating the genetic behavior of the bacteria. Here you can read more extensively about quorum sensing and its influence in phatogenity.

The Tragedy of the Commons and the “cheatobiotics”

But not everything works as planned, even in the bacterial world: “There are some rotten apples among us, folks!”. Some bacteria don’t produce signal molecules, and don’t contribute to the biofilm formation, although they get all the benefits of living in this public system. This mutation occurs naturally in very competitive environments, and not only in bacteria. So, these unethical bacteria prosper nicely in this ambient in fact. Things don’t unfold so well for the community, though. As we can see in the figure, the growth is slowed when the red selfish bacteria are present.

This problem is usually called “The tragedy of the commons” in economics. Bacteria have several ways in nature for evading the problem, like kin selection: the more related you are to your neighbors the more likely is that you will cooperate with them, favoring your DNA and the cooperative genome persistence. You can read further about this matter here, and how this kin selection seems harder in a very competitive ambient. And here you have the study of the cheaters influence in biofilm formation from where the figure was taken.

But, aside from the bacterial-social implications we can conclude from this curious situation, there is something very interesting we can do with these cheaters.

Biofilms of pathogenic bacteria develop chronic infections in patients, presenting a very difficult treatment. Bacteria in biofilm phenotype acquire antibiotic tolerance through several mechanism, and the inmune system has a very hard time trying to attack the microorganisms inside this thick structural matrix. This biofilm infections are a feared complication in any prosthetic implant, in cystic fibrosis patients, and they seem to be related with otitis media and other chronic infections, as you can see here.

And your enemy’s enemy is…not so enemy as your enemy. I mean, being biofilm formation the problem here, what if we give these bacteria some cheating mutant partners? So, infecting the patient with new mutant cheating bacteria may look like anything but a cure, but there is serious work around this idea. Nature reported about this here, where we can find that this called “cheatobiotics” have been tested even in vivo with good results.

I don’t know if we will see cheatobiotic vials in the near future, but it seems interesting enough to keep an eye on it. What do you think are the odds? Did you know about biofilm and chronic infections? I need to say thank you to these Copenhagen University course professors for the many things I have learned about this matter completing the course. If you are deeply interested give it a try. Coursera have free tons of knowledge.  I hope you liked the post, thank you for reading and see you soon!