“Le bonheur, c’est les autres”
To live at the expense of others is harmful to the common welfare. This is also true for the simplest of organisms − bacteria. And thus, strategies have been developed to keep those who cheat under control. The new SNSF Professor Médéric Diard studies how bacterial communities evolve and cooperate. He could also be described as a “sociologist” for bacterial communities.
You work in infection biology. What are the most important questions you are dealing with?
The big question of my research is to understand the evolution of virulence in pathogens with a focus on enteropathogenic bacteria. I work with the diarrhea-causing bacterium, Salmonella Typhimurium. The advantage of this model organism is that the mechanisms of infection and virulence are well known. And the fact that these bacteria also infect mice makes them very attractive. With this model we can see the evolution in action.
And how do they evolve?
In the last nine years in the Hardt Lab at the ETH Zürich, I was focusing on the dynamics of within-host evolution of S. Typhimurium. We discovered that these pathogens tend to lose their virulence during growth in the gut.
But this doesn’t seem to be a good survival strategy?
That’s true. But evolution is a short sighted process. The fastest growing mutants will win the competition whatever the consequences. The production of virulence factors such as molecular injection needles is very energy consuming and associated with much lower growth rates. This means it is a huge cost for the bacteria to trigger the infection, and therefore, a tendency for mutants to evolve that have lost the ability to express these virulence factors. We call them “cheaters”. They can grow fast because they profit from the welfare of the community without paying the costs. I like to use this metaphor of sociobiology.
And how can the community protect itself from these cheats?
The avirulent cheaters invade the population, leading to an instability in the virulence of salmonella. This would be a disaster for the community if the virulent pathogens would not have evolved a solution to get rid of these invaders. But indeed, the emergence of cheaters raised the question of how salmonella can exist as a virulent bug. What we have observed is that salmonella cultivates the division of labor.
In what way?
If you look at a population in a natural environment you will find two different phenotypes; the “on-cell” that expresses virulence factors and the one that does not. These two types can epigenetically switch from one to the other. In a normal population we have virulent but slow-growing on-cells and fast-growing non-virulent “off-cells”. The job of the on-cells is to get rid of the gut microbiota by inducing inflammation and thus to construct a niche. However, a population with many on-cells also promotes the emergence of the constantly “locked-off” cheaters. Once the cheaters have squeezed out their virulent competitors, the innate immune system stops inflammation and the microbiota restart growth. Salmonella loses, because it can’t colonize the gut without inflammation. The job of the off-cells seems therefore to compete with the arising cheaters and to protect the niche. These off-cells could be very important for the transmission of virulent Salmonella. I think that the division of labor is crucial for the survival of the whole population.
How can your research help find novel strategies to fight bacterial infections?
Our aim is not to develop new antibiotics. With antibiotics you always push the evolution in a direction of emergence of new resistance. To avoid any misunderstanding, we should keep moving on to look for new drugs. But we should also think about alternatives. The point is, if we know how pathogens evolve, we could be one step ahead. In the case of Salmonella, it means that we could create a beneficial environment for the harmless cheaters and thus protect the host from invasion by virulent bacteria. That’s classical biocontrol – you keep the niche occupied by something you can control. This is not a total protection of one host, but you can disrupt the transmission chain. This can be reinforced by vaccination. Here we are working in collaboration with the Slack Lab at the ETH. In this sense, we try to work with evolution, not against it.
You are now, for the first time, an independent research group leader. How does it feel?
It's a big step. My former group was fantastic and I hope I can manage to build up such a team with enthusiastic people and have lively discussions. The most important aspect in research is to work in a collaborative environment. I am convinced that also here a division of labor is the key to success.
Why did you choose the Biozentrum?
I had several options. But the Biozentrum is one of the top three institutes in Switzerland to link molecular biology research and study the evolution of virulence. And experiencing the transition of the institute is also really exciting: the new director, the new building and a new strategy. Now I can directly see the Biozentrum’s evolution in action.
You are a technician by training. Was it clear from the beginning that you would study further?
When I was a child, I wanted to become paleontologist. But my mom told me “no, that’s just a hobby; get a real job” (he laughs). So, I chose a scientific curriculum ensuring quick access to the job market, technician biochemist. After the certificate, I was good enough to enter the university directly at the master’s level, and I knew by then that academia was my thing. I went for it. My job is now my hobby. I feel privileged.
You were born and raised in France. What is the typical French lifestyle, and do you celebrate it?
It is difficult to define one typical French lifestyle. Of course, French food and wine are great, but what I really enjoy in France is the diversity of landscapes, people and ideas. To a certain extent, you also have diversity in Switzerland. This is especially true in Basel where you can have what’s best from three countries. The way of living is relaxed but efficient. I like it. I could feel like home here.
In July, Médéric Diard started as a new SNSF Professor at the Biozentrum. After his training as a Laboratory Technician, he studied biochemistry and microbiology at the Paris Diderot University where he also earned his PhD in 2008. From 2009 to 2018, he carried out research as a postdoctoral fellow in the group of Prof. Hardt at the ETH Zurich. Last year, he was awarded the Robert Koch Postdoctoral Award and the Encouragement Award of the Swiss Society for Microbiology for his outstanding research.