Targeting antibiotic-resistant bacteria specifically and promptly
The spread of antibiotic-resistant bacteria is cause for concern–and no longer constitutes a problem that only hospitals face. In the current issue of Science, DZIF scientists from the University of Tübingen call for developing active agents that selectively fight these resistant bacteria before they cause infections. We spoke to one of the authors, Prof Andreas Peschel, about this strategy.
You see the danger of a post-antibiotic era occurring, in which effective antibiotics are no longer available. How high is the danger of this happening at the moment?
Andreas Peschel: In many countries of the world, also our neighbouring countries, we are observing that, for some pathogens, there are hardly any effective antibiotics available, and that especially highly resistant gut pathogens cause infections that have become almost untreatable. We also have such cases in Germany, and outbreaks keep occurring and there have been a few cases of death. This is not a dramatic problem at the moment, but the numbers are increasing. We have to expect that this will develop into a threatening situation in a few years. The other problematic issue: it no longer involves only hospital pathogens, but the resistant bacteria are now also occurring in the population. So we have a paradigm shift that is currently not yet being perceived as such. Our article in Science discusses the issue from this angle for the first time.
You and your colleagues suggest focussing on agents that selectively target resistant bacteria, before they cause infections. What does this mean?
Andreas Peschel: We are all talking about the need for new drugs, which we are support of. However, we have one additional point: we not only need antibiotics to treat infections, but we also see that the majority of infections are caused by pathogens we are already carrying in our bodies. Healthy people, and, particularly immunocompromised risk patients already carry these pathogens in the gut and also in the nose, an example being Staphylococcus aureus. In cases of severe infections, usually a pathogen that was previously already in the body is involved. This offers new possibilities for prevention: in future, patients could and should be screened earlier for these pathogens.
Which bacteria do we need to fear?
Andreas Peschel: The classic pathogens are so-called MRSA strains, i.e. methicillin-resistant Staphylococci, in the nose. Here, a further increase in the spread has been prevented, which has been a success. However, different kinds of new gut bacteria are now also involved, e.g. Escherichia coli, Klebsiella, Enterobacter and others. They carry new classes of resistance genes, and often, when they occur in combination with other types of resistance, no alternative treatment is available.
How is this problem currently being dealt with? What control measures exist?
Andreas Peschel: This strongly depends on the individual hospitals and, of course, also on the country. Systematic screening for these new gut bacteria has not existed to date. We are observing an increase in numbers. And this is our crucial point: when you identify a patient who is colonised by a highly resistant pathogen like this, what do you do with him/her? Do you isolate him to protect other patients? This in itself is already very controversial, because we do not know much about how the pathogen spreads and whether other patients are actually protected by this isolation. But what can you do with the patient, how can the resistant pathogens be eliminated, or as we would say in professional terms, how could we decolonise him? And this is the strategy we suggest: to decolonise risk patients.
What exactly does the term decolonisation mean?
Andreas Peschel: Decolonising agents are going to be very important in future, because they are preventive. One would screen risk patients for these resistant bacteria in the gut or nose before they undergo chemotherapy or major surgery. Then methods of getting rid of these pathogens and eliminating them from the patient would be needed. In order to do this, we need new types of agents that, in contrast to antibiotic agents, do not have broad-spectrum effects but have a targeted effect on these three or four specific types of bacteria.
How could agents like this act?
Andreas Peschel: We are working on two projects at the DZIF, which serve as good examples. We are conducting our investigations on Staphylococcus aureus, but the concept is transferrable to gut bacteria as well. One example is the group of bacteriophages, i.e. viruses that enter bacteria and are very specific for certain types of bacteria. Then one could specifically target, for example Staphylococcus aureus, with a phage lysine. If you apply this enzyme to the nose, only that one type of bacteria will be destroyed, and all other types residing in the nose will not be affected. The second example is the group of bacteriocins. These are antimicrobial molecules produced by specific types of bacteria to kill competing bacteria. We discovered Lugdunin, for example, which is produced by a type of bacteria found in the nose and fights Staph. aureus. This could be used as a new probiotic strategy. We could look for precisely such bacteria in the gut, to get rid of other pathogens.
New broad-spectrum antibiotics are not being expected for the coming years. How quickly could your suggested decolonisation agents called into action?
Andreas Peschel: We cannot say for the moment. We will surely make advances over the next years because we have a lot of ongoing projects, at the DZIF as well. The Science article mainly aims at initiating the discussion. The concept has not yet been fully taken up by the pharmaceutical industry and we often hear that it is not lucrative enough. We counter this with the fact that the number of patients colonised by antibiotic-resistant pathogens is going to increase dramatically worldwide; there are many more colonised patients than there are infected ones. We hope to motivate more companies to focus on these specific agents.
Which further steps do you consider necessary to gain control over the antibiotic resistance problem in the next years?
Andreas Peschel: We need to remain active on different fronts. We also need to develop broad-spectrum antibiotics. We need to develop this new class of closely meshed agents which we need for decolonisation and, alongside this, we need additional clinical trials that contribute towards a general understanding. Some of these are already being conducted at the DZIF. For example, we need to find out if and how the pathogens spread between patients. And another major point is: if we are all carrying these pathogens, where do they actually come from? There are many indications that they come from animal feed, because in Europe we use over 10,000 tonnes of antibiotics in animal feed, which are also needed by us humans. We also need to understand the reservoirs and disrupt the chain. To conclude, perhaps the most important point again: these pathogens do not come from nowhere. We need to stop the spread and develop new agents that we can use for decolonisation.
