Quest for bacterial cocktails to fight infections

Date:
October 12, 2021
Source:
German Center for Infection Research
Summary:
The intestines of a healthy person contains hundreds of
different bacteria that provide efficient protection against
infections. However, if the equilibrium of this community, known
as the microbiota, is disturbed -- for example, due to antibiotic
therapy -- pathogens such as salmonella or multiresistant hospital
germs such as Klebsiella pneumoniae can gain the upper hand --
sometimes with severe consequences for those affected. Scientists
have been researching the interaction of intestinal bacteria and
have recently identified bacterial strains that play a special
role in two studies.



FULL STORY ==========================================================================
Most people have already experienced first-hand how important
a healthy microbiome is when they had to take a broad-spectrum
antibiotic. Unfortunately, the drug does not only destroy the
pathogens. It also affects the 'good' bacteria in the bowel that otherwise occupy the most important niches and help fend off pathogens. This
protective mechanism is called colonisation resistance. But which
bacterial species are 'good', or 'commensal' in technical terms, and
how can they protect against colonisation, i.e. how can they prevent
pathogens from settling? Prof. Till Strowig, HZI, and Prof. Ba"rbel
Stecher, LMU Mu"nchen, decided to take a closer look at these questions.


========================================================================== Klebsiella pneumoniaehas a strong opponent The intestinal inhabitant
Klebsiella pneumoniae is one of the most dreaded 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 facilitate further infections. In collaboration with partners
in Magdeburg and Hannover, the HZI department led by Till Strowig, was
able to isolate strains of a related bacterium from the intestine that
are highly effective against K. pneumoniae. This species, identified as Klebsiella oxytoca, uses the same sugars as the pathogen, but it does
it more efficiently so that there is not enough left for the pathogen
to survive. "K. oxytoca can specifically force out multiresistant
K. pneumoniae bacteria because it effectively blocks the niche to be
occupied by the hospital germ," explains Strowig. The scientists were also
able to show in mice that these bacteria help the bacterial composition
inside the intestines regenerate more quickly after antibiotic therapy
and ensure that protection against infections is restored.

"First we wanted to find out how susceptible healthy adults and children
are to colonisation with multi-resistant K. pneumoniae bacteria," says
lead author Lisa Osbelt to explain the study approach. For this study,
the scientists took stool samples from 100 healthy people and incubated
them with the germ overnight. The next day, the growth of the bacteria was measured. It revealed a great variability in the colonisation depending
on each individual's microbial community in the intestine. Next, the
group examined the samples in which the germ had grown poorly; in many
of them K. oxytoca could be identified. The researchers then tested the behaviour of the two 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 colonised with different
groups of bacteria (12 bacterial strains in total), three additional
strains cooperated with K. oxytoca for the protective effect.

How 'good' E. colibacteria can protect against salmonella infection
One of the best-known bacteria in the human gut is Escherichia coli,
or E. coli for short. It is frequently mentioned in headlines as a 'bad' bacterium because it is considered an indicator of faecal contamination
of drinking water, and certain variants can cause infections. But the
bacterium has many different strains and, besides the pathogenic variants, there are also commensal representatives. However, so far little is known
about the role of these variants for human health. Ba"rbel Stecher and her
team at the Max von Pettenkofer-Institute at the LMU found out some time
ago that commensal E. coli protect against salmonella infection. Again,
it is their sugar consumption that limits the growth of the salmonellae
by depriving them of food.

In the current study, the researchers were able to demonstrate that this protective effect of E. coli also depends on the microbial environment
in the gut. This means that it depends on which microorganisms are
still present, in other words, whether E. coli is in good company. "If
there are lachnospiraceae present in our model that can also metabolise
simple sugars, E. coli can provide protection -- otherwise, it can't,"
explains Stecher. She adds: "Overall, we now understand better why
probiotics may also help in some people but not in others. The reason
for it is the microbial environment, which varies greatly from person
to person." About mice and men: a step towards 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 investigate the colonisation and influence of pathogens in a specifically targeted manner. A synthetic cocktail of 12 bacterial strains colonises germ-free mice stably over several generations and forms an intestinal microbiota representative of mice.

Both studies involving Klebsiella and E. coli respectively use this model
to carefully identify the interdependencies in the intestinal flora. But
even in mice, it becomes clear how complex the interdependencies
are. However, the studies of the microbiota researchers give us hope,
because they show once again that we are on the right track with regard
to the processes in the intestine.

"The use of live bacteria, so-called probiotics, for the treatment of
patients with existing colonisation and as preventive administration
after antibiotic therapy is generally conceivable', says Till Strowig confidently. Ba"rbel Stecher adds: "The utilisation of a broad sugar
range plays a major role for the design of these bacterial cocktails,
and a protective cocktail must always contain more than one bacterium." ========================================================================== Story Source: Materials provided by
German_Center_for_Infection_Research. Note: Content may be edited for
style and length.


========================================================================== Journal References:
1. Lisa Osbelt, Marie Wende, E'va Alma'si, Elisabeth Derksen,
Uthayakumar
Muthukumarasamy, Till R. Lesker, Eric J.C. Galvez, Marina
C. Pils, Enrico Schalk, Patrick Chhatwal, Jacqueline Fa"rber,
Meina Neumann-Schaal, Thomas Fischer, Dirk Schlu"ter, Till
Strowig. Klebsiella oxytoca causes colonization resistance against
multidrug-resistant K. pneumoniae in the gut via cooperative
carbohydrate competition. Cell Host & Microbe, 2021; DOI:
10.1016/j.chom.2021.09.003
2. Claudia Eberl, Anna S. Weiss, Lara M. Jochum, Abilash Chakravarthy
Durai
Raj, Diana Ring, Saib Hussain, Simone Herp, Chen Meng, Karin
Kleigrewe, Michael Gigl, Marijana Basic, Ba"rbel Stecher. E. coli
enhance colonization resistance against Salmonella Typhimurium
by competing for galactitol, a context-dependent limiting carbon
source. Cell Host & Microbe, 2021; DOI: 10.1016/j.chom.2021.09.004 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211012091858.htm

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