In search of bacterial cocktails to fight infections

The intestinal inhabitant Klebsiella pneumoniae is one of the most feared hospital germs.


Prof. Dr. Till Strowig

Prof. Dr. Barbel Stecher

Hundreds of different bacteria cavort in the intestine of a healthy person and efficiently protect against infections. However, if the balance of this community, known as the microbiota, is disturbed – for example, by antibiotic therapy – pathogens such as Salmonella or multidrug-resistant hospital germs like Klebsiella pneumoniae gain the upper hand – with sometimes severe consequences for the affected persons. DZIF scientists at the Helmholtz Centre for Infection Research (HZI) and the Max von Pettenkofer Institute at LMU Munich are investigating the interaction of intestinal bacteria and have recently identified bacterial strains that play a special role in two studies. They report on their findings in two independent studies in the scientific journal Cell Host& Microbe.

How important a healthy microbiome is, most people have already experienced first hand when they had to take a broad-spectrum antibiotic. The drug not only destroys the pathogens, but also the "good" bacteria in the intestine, which otherwise occupy the most important niches and help to prevent pathogens from entering. This protective mechanism is known as colonization resistance. But which bacterial species are "good" or in technical jargon "commensal" and how can they protect against colonization, i.e. colonization by pathogens?? Prof. Dr. Till Strowig, HZI, and Prof. Dr. Barbel Stecher, LMU Munich, have taken on these questions and taken a closer look.

Klebsiella pneumoniae has a strong opponent

The intestinal inhabitant Klebsiella pneumoniae is one of the most feared hospital germs, as it can cause severe pneumonia, urinary tract infections or even sepsis in weakened patients. It is increasingly resistant to common antibiotics and can promote further infections. The department led by Till Strowig at the HZI, together with partners in Magdeburg and Hannover, was able to isolate strains of a related bacterium from the intestine that are highly effective against K. pneumoniae are. This as Klebsiella oxytoca identified species uses the same sugars as the pathogen, but so efficiently that the pathogen is left with too few to survive. "K. oxytoca can be multiresistant K. pneumoniae-bacteria specifically, as it effectively blocks the niche to be occupied by the hospital germ," explains Strowig. The scientists were also able to show in a mouse model that these bacteria help the bacterial composition in the intestine regenerate more quickly after antibiotic therapy and restore protection against infections.

"We first wanted to find out how susceptible healthy adults and children are to colonization with multidrug-resistant K. pneumoniae-bacteria," says first author Lisa Osbelt, explaining the study’s approach. For this purpose, the scientists took stool samples from 100 healthy individuals and incubated them with the bacteria overnight. The next day, the growth of the bacteria was measured. The colonization showed great variability depending on the individual microbial community in the gut. In a further step, the group then examined the samples in which the germ had grown poorly, and here it was always possible to find K. oxytoca be identified. Researchers then tested the behavior of both bacteria in different mouse models and found that the addition of K. oxytoca can significantly reduce susceptibility to the hospital germ. When germ-free mice were colonized with different groups of bacteria (12 bacterial species in total), three additional species also showed a protective effect.

How "good E. coli-Bacteria can protect against salmonella infection

One of the best known bacteria in the human intestine is Escherichia coli, briefly E. coli Called. It often hits the headlines as a "bad" bacterium because it is considered an indicator of fecal contamination of drinking water and certain variants can cause infections. But the bacterium has many different strains, and in addition to pathogenic variants, there are also commensal representatives. Little is known, however, about the role of these in human health. Barbel Stecher and her team at the Max von Pettenkofer Institute at Ludwig Maximilian University discovered some time ago that commensal E.coli protect against salmonella infection. Again, it is their sugar consumption that puts Salmonella in its place by depriving them of food.

In the current study, the researchers were able to show that this protective effect of E. coli also depends on the microbial environment in the intestine. That is, it depends on which microorganisms are still present, whether they are E. coli are thus found in good company. "If there are salmonospiraceae present in our model that can also metabolize simple sugars, it can E. coli protect – otherwise not," explains Stecher. And adds, "Overall, we now better understand why probiotics may also help well in some people but not others. The reason for this is the microbial environment, which varies greatly from person to person."

From mice and humans: On the way to a protective bacterial cocktail?

Studying hundreds of bacteria and other microorganisms of the microbiota for their effects is an incredibly complex undertaking even in mice. With their mouse model developed in Munich, the scientists can specifically investigate the colonization and the influence of pathogens. A synthetic cocktail of 12 bacterial species colonizes germ-free mice stably over several generations and forms an intestinal flora that is representative for mice. Both the studies on Klebsiella as well as to E. coli use this model to approach interactions in the intestinal flora. But even in mice, it becomes clear how complex the relationships are. However, the studies of the microbiota researchers give hope, because they show once again that the processes in the intestine are being tracked down in detail.

"The use of live bacteria, sog. Probiotics, for the treatment of patients with an existing colonization and as preventive administration after antibiotic therapy is generally conceivable," says Till Strowig confidently. And Barbel Stecher adds, "In the design of such bacterial cocktails, the utilization of a broad spectrum of sugars plays a major role, and a protective cocktail must always contain more than one bacterium."

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