 The basic question that we are asking is, where do bacterial pathogens come from? And this sounds like a trivial question, but it is not trivial and it's not easy to answer because it's entirely different from what we know about viruses. So the COVID-19 pandemic has taught us that most of the viral infections they're coming from outside with air or whatever, this is different from most of the severe bacterial pathogens because at some point they're coming in, but they're already with us long before the infection is starting. There are members of what we call the microbiome, so the microbial communities that are colonizing our body surfaces, our gut, but also our respiratory tract and skin. In some, it's a small minority, but some of these bacteria that we are carrying around, they are the pathogens that are at a later time point causing severe infections. And they are particularly dangerous when they carry antibiotic resistance genes because then they are very difficult to treat. So this is an important realization. Most of these pathogens are coming from the inside and we are often carrying them around with us. And the second thing is, not everybody is colonized by these pathogens, only some of us. And when we are not colonized, it is probably because we have the right beneficial bacteria with us that are eliminating the pathogens and make it very difficult for them to colonize our microbiomes. That brings us to our research. We would like to understand which are the good bacteria, which mechanisms are they using to eliminate the pathogens. And once we understand the mechanisms, can we use these bacteria as kind of precision probiotics that we can bring in to a risk patient to relieve them from the risk of an infection? And can we use their antimicrobial compounds to develop new drugs that we can use for smarter antibiotics for better prevention and treatment of bacterial infections in the future? Understanding how potentially beneficial bacteria may interfere with the colonization capacities of pathogens is an ecological approach. We're learning a lot from environmental scientists when we're trying to understand the dynamics of pathogens now. And this is a very interesting interdisciplinary approach, I can say. It starts on a descriptive level. Of course, we first need to understand how a microbiome is composed and how different it may be in a person that is colonized by pathogen or not colonized. We have to extract the differences. And it starts with a metagenome sequencing approach. So we're isolating DNA from different persons who are colonized are not sequencing all the DNA of these bacteria, which is a huge amount of data that we are generating. We need some bioinformatic approaches and colleagues also here in Tubingen who are helping us with that. One of the challenges here is to get enough DNA. This is comparatively easy for the gut where you get unlimited amount of samples if you want, but looking at your nose or your skin. And this is what we are mostly doing in our group because we're looking at pathogens that are living in the human nose. That is challenging because you only get tiny amounts of DNA and you need to find ways to amplify it and to work with the lowest possible amount of DNA. And once we have the metagenome data, we come to the next step and this means we are generating hypotheses. So we are looking at the capacities of all these bacteria, the molecular, biochemical, immunological properties of these microbes and come up with hypotheses what a beneficial bacterium might do to interfere with the colonization capacity of a pathogen. And once we have this hypothesis, we can make a bacterial mutant that helps us in the next step and the functional approach to verify if this mechanism, this bacteria is truly responsible for the pathogen-eliminating capacity. That brings us to the third step which is probably the most difficult. We want to simulate the competition between these bacteria in real-life situation in a situation where you simulate the complexity of a human microbiome with all these dozens, hundreds or thousands of bacteria species and there we have to go a long way because we are starting from scratch often in particular with the microbiomes that we are looking at to come up with real realistic model systems that can start with a culture in a bacterial cultivation medium where we bring in a couple of these bacteria and a reduced complexity and can go up to a full complexity of a human microbiome in a human clinical trial where we use human volunteers who we know are colonized by a specific pathogen and who we can then colonize with beneficial bacteria hoping that these bacteria will eliminate the pathogen in these human volunteers. All the different bacterial pathogens, we are focusing on one specific bacterium that is colonizing the human nose. This is Staphylococcus aureus, antibiotic-resistant variant of it is called metacillin-resistant Staphylococcus aureus or MRSA, a bacterium that is causing huge problems in our hospitals, many infections that are very difficult to treat. We looked at the microbiomes of many humans of those that are colonized are not colonized. 70% of the human population is not colonized by Staphylococcus aureus and we found that in these humans there is another bacterial species over-represented that is called Staphylococcus luctonensis and these bacteria carry the genes for the production of a new type of antimicrobial compounds, so the new antibiotic that has never been characterized before. We called it luctonin and obviously these bacteria are producing it and the human nose that kills Staphylococcus aureus and then you have a six-fold lower risk to be colonized by Staphylococcus aureus and also lower risk than to develop an invasive infection. We are characterizing luctonin now because it's the first member of a new class of antibiotics. We are starting to understand how it kills Staphylococcus aureus. We are optimizing the compound also a bit so we can go into drug development and we have a patent for luctonin. We can think about using it in the future for the development of a new type of antibiotic. We're thinking about using Staphylococcus luctonensis or commensal, a beneficial bacteria to develop something that we call a precision probiotic. You would bring in these bacteria to the nose of a risk patient to hopefully eliminate Staphylococcus aureus. So infections caused by antibiotic resistant bacterial pathogens will be the next pandemic. These bacteria are causing already 700,000 deaths per year globally at the moment and we're calculating that there will be several million deaths in the next 10 or 20 years if we are not finding better ways to deal with these pathogens in the future. There are several aspects to focus on in terms of research. On one end we need to keep the numbers of resistant bacteria as low as possible because they're hiding in our microbiomes. We have to find ways to keep the numbers low and this is what we are doing with understanding how we can eliminate these antibiotic resistant pathogens in our microbiomes. Second thing is we need new antimicrobial compounds so we can treat even the infections caused by antibiotic resistant bacteria. Here we have another problem. The pharmaceutical companies, most of them have abandoned their development programs for new antibiotics. They're focusing more on chronic diseases where they get better returns on their investments. We can step in here a bit with our academic research. Luctonine is a good example that has the capacity to become a new drug to treat also an MRSA or other resistant bacteria. And the third thing is simply developing new traditional antibiotics will also not solve the problem. We need smarter antibiotics that are not damaging our microbiomes as a whole. We need smart antibiotics that are focusing on the pathogens and are eliminating those while preserving the integrity of the microbiomes because that will create less lecture pressure for the development of resistances. So the big vision is personalized medicine based on all the information that we get from the genetic information of our microbiomes from the metagenomes. If we analyze the sequence of our microbiomes regularly in the future, we will get a lot of information about the risk for specific diseases, for antibiotic resistant bacterial infections. If we are colonized by these bacteria or also for other diseases that may be caused by the disbalance of a human microbiome. That will on one hand help us to prevent the looming post-antibiotic era. If we find new ways to eliminate the resistant pathogens and develop new drugs to reach these goals, we need an interdisciplinary approach. It's not enough for me as a microbiologist to do my own research. I need my colleagues from other disciplines, computational, clinical and compound focused scientists to do all these things in a joint approach. We're doing that here in Tübingen with our cluster of excellence that is called controlling microbes to fight infections. We're getting funded by the German state for seven years to do this interdisciplinary platform on research against bacterial infections and other diseases that all are caused and affected by human microbiome composition.