Kiel Life Science

Bacteria as pacemaker for the intestine

Nov 22, 2017

CAU research team discovers connection between microbiome and tissue contractions that are indispensable for healthy bowel functions

Spontaneous contractions of the digestive tract play an important role in almost all animals, and ensure healthy bowel functions. From simple invertebrates to humans, there are consistently similar patterns of movement, through which rhythmic contractions of the muscles facilitate the transport and mixing of the bowel contents. These contractions, known as peristalsis, are essential for the digestive process. With various diseases of the digestive tract, such as severe inflammatory bowel diseases in humans, there are disruptions to the normal peristalsis. To date, very little research has explored the factors underlying the control of these contractions. Now, for the first time, a research team from the Cell and Developmental Biology (Bosch AG) working group at the Zoological Institute at Kiel University (CAU) has been able to prove that the bacterial colonisation of the intestine plays an important role in controlling peristaltic functions. The scientists published their results yesterday - derived from the example of freshwater polyps - in the latest issue of Scientific Reports.

The triggers for the normal spontaneous contractions of the muscle tissue are so-called pacemaker cells of the nervous system. In a specific rhythm and without any external stimulation, they emit electrical impulses, that ultimately reach the smooth muscles of the intestinal wall, and cause them to contract. Although the impulses as such occur by themselves, their frequency and intensity, however, are subject to external influences. "The example of the simple freshwater polyp Hydra has shown us that the bacterial colonisation of the organism can affect the contractions of its digestive cavity. Most likely they do so by modulating the underlying pacemaker signals," said Professor Thomas Bosch, head of the study and spokesperson for the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms". Unlike other more complex organisms, Hydra have no bowel in the true sense of the word. Their simple body cavity assumes, amongst other things, the function of a digestive tract; the surrounding tissue also exhibits the typical contractions associated with more highly-developed intestines.

To find out how peristalsis is regulated in the freshwater polyps, the researchers compared normal Hydra which had typical bacterial colonisation with those that had their microbiome completely removed with an antibiotic cocktail. In comparison, these organisms without bacterial colonisation - also referred to as germ-free polyps - exhibited a reduction in contractions by about half. At the same time, the rhythm of the movements became disrupted, and some of the breaks between the contractions were much longer. Thus, the absence of the typical microbiome in Hydra compromised the peristaltic movements in the body cavity.

In a further step, the scientists restored the specific bacterial colonisation in the germ-free organisms. Initially, they introduced each of the five most common bacterial species found in the Hydra microbiome individually back into the sterile polyps. It turned out that this individual bacterial colonisation has no appreciable effect on the frequency and timing of contractions. Only the joint re-introduction of the five main representatives of the microbiome led to a marked improvement in peristalsis, although even then, the pattern of contractions was not fully normalised. Interestingly, an extract produced from the colonising bacteria had a similarly positive influence.

From these observation the Kiel research team concluded that only the natural Hydra microbiome - characterised by a balance between the bacterial species present - can play an important pacemaker role in peristalsis. They discovered that, in this case, certain molecules secreted by the bacteria can intervene in the control mechanism of the pacemaker cells. As such, bacterial signals can have a decisive effect on the pattern of spontaneous peristaltic contractions. "We were able to demonstrate for the first time that in our simple model organism, the microbiome has an indispensable function in the frequency and timing of tissue contractions," emphasised Bosch.

In addition, the example of the evolutionarily ancient model organism Hydra shows us that the control of vital processes of multicellular organisms by their bacterial symbionts already originated very early in the evolution of life, continued Bosch. These ground-breaking results are especially promising for medical research: "The fundamental explanation of the cooperation between organism and microbiome in regulating peristalsis will in future help us to understand the emergence of severe diseases, which arise from disrupted movement of the intestine," summarised Bosch.

Original publication:
Andrea P. Murillo-Rincón, Alexander Klimovich, Eileen Pemöller, Jan Taubenheim, Benedikt Mortzfeld, René Augustin & Thomas C.G. Bosch (2017): “Spontaneous body contractions are modulated by the microbiome of Hydra”. Scientifc Reports, Published on 21.11.2017,
doi:10.1038/s41598-017-16191-x

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-368-1.gif
Caption: The typical contraction pattern of the freshwater polyp Hydra: Contraction and relaxation of the same animal over the course of three minutes.
Animation: Andrea Murillo-Rincon, Dr. Alexander Klimovich

www.uni-kiel.de/download/pm/2017/2017-368-2.jpg
Caption: Body contractions in Hydra are triggered by nerve cells (in green), while bacteria (rod-shaped cells in red) influence the underlying pacemaker activity.
Image: Christoph Giez, Dr. Alexander Klimovich

www.uni-kiel.de/download/pm/2017/2017-368-3.jpg
Caption: Hydra’s nerve cells (in green) generate electrical impulses that cause contractions of muscle fibers (shown in red) in the gastric cavity wall.
Image: Christoph Giez, Dr. Alexander Klimovich

Contact:
Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: 0431-880-4170
E-Mail: tbosch@zoologie.uni-kiel.de

More information:
Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Cell and Developmental Biology (Bosch group), Zoological Institute, Kiel University
www.bosch.zoologie.uni-kiel.de

New approach to antibiotic therapy is a dead end for pathogens

Jun 01, 2017

Kiel-based team of researchers uses evolutionary principles to explore sustainable antibiotic treatment strategies

The World Health Organization WHO is currently warning of an antibiotics crisis. The fear is that we are moving into a post-antibiotic era, during which simple bacterial infections would no longer be treatable. According to WHO forecasts, antibiotic-resistant pathogens could become the most frequent cause of unnatural deaths within just a few years. This dramatic threat to public health is due to the rapid evolution of resistance to antibiotics, which continues to reduce the spectrum of effective antibacterial drugs. We urgently need new treatments. In addition to developing new antibiotic drugs, a key strategy is to boost the effectiveness of existing antibiotics by new therapeutic approaches.

The Evolutionary Ecology and Genetics research group at Kiel University uses knowledge gained from evolutionary medicine to develop more efficient treatment approaches. As part of the newly-founded Kiel Evolution Center (KEC) at Kiel University, researchers under the direction of Professor Hinrich Schulenburg are investigating how alternative antibiotic treatments affect the evolutionary adaptation of pathogens. In the joint study with international colleagues now published in the scientific journal Molecular Biology and Evolution, they were able to show that in the case of the pathogen Pseudomonas aeruginosa, the evolution of resistance to certain antibiotics leads to an increased susceptibility to other drugs. This concept of so-called "collateral sensitivity" opens up new perspectives in the fight against multi-resistant pathogens.

Together with colleagues, Camilo Barbosa, a doctoral student in the Schulenburg lab, examined which antibiotics can lead to such drug sensitivities after resistance evolution. He based his work on evolution experiments with Pseudomonas aeruginosa in the laboratory. This bacterium is often multi-resistant and particularly dangerous for immunocompromised patients. In the experiment, the pathogen was exposed to ever-higher doses of eight different antibiotics, in 12-hour intervals. As a consequence, the bacterium evolved resistance to each of the drugs. In the next step, the researchers tested how the resistant pathogens responded to other antibiotics which they had not yet come into contact with. In this way, they were able to determine which resistances simultaneously resulted in a sensitivity to another drug.

The combination of antibiotics with different mechanisms of action was particularly effective - especially if aminoglycosides and penicillins were included. The study of the genetic basis of the evolved resistances showed that three specific genes of the bacterium can make them both resistant and vulnerable at the same time. "The combined or alternating application of antibiotics with reciprocal sensitivities could help to drive pathogens into an evolutionary dead end: as soon as they become resistant to one drug, they are sensitive to the other, and vice versa," said Schulenburg, to emphasize the importance of the work. Even though the results are based on laboratory experiments, there is thus hope: a targeted combination of the currently-effective antibiotics could at least give us a break in the fight against multi-resistant pathogens, continued Schulenburg.

Original publication:
Camilo Barbosa, Vincent Trebosc, Christian Kemmer, Philip Rosenstiel, Robert Beardmore, Hinrich Schulenburg and Gunther Jansen (2017): Alternative Evolutionary Paths to Bacterial Antibiotic Resistance Cause Distinct Collateral Effects. Molecular Biology and Evolution
doi.org/10.1093/molbev/msx158

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-171-1.jpg
Caption: The pathogen Pseudomonas aeruginosa during the evolution experiment in the laboratory.
Image: Camilo Barbosa/Dr. Philipp Dirksen

www.uni-kiel.de/download/pm/2017/2017-171-2.jpg
Caption: Doctoral student Camilo Barbosa examined the effect of "collateral sensitivity", which can make antibiotic-resistant bacteria treatable.
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2017/2017-171-3.jpg
Caption: The research team analysed a total of 180 bacterial populations of the pathogen Pseudomonas aeruginosa.
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2017/2017-171-4.jpg
Caption: The bacteria became resistant to certain antibiotics, but at the same time sensitive to other substances.
Photo: Christian Urban, Kiel University

Contact:
Prof. Hinrich Schulenburg
Spokesperson “Kiel Evolution Center” (KEC), Kiel University
Tel.: +49 (0)431-880-4141
E-mail: hschulenburg@zoologie.uni-kiel.de

More information:
Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Evolutionary Ecology and Genetics research group, Zoological Institute, Kiel University:
www.uni-kiel.de/zoologie/evoecogen

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni Text / Redaktion: ► Christian Urban

 

Switching mutations on and off again

Apr 12, 2016

Kiel research team facilitates functional genomics with new procedure

 

Mould is primarily associated with various health risks. However, it also plays a lesser-known role, but one which is particularly important in biotechnology. The mould (ascomycete) Aspergillus niger, for example, has been used for for around 100 years to industrially produce citric acid, which is used as a preservative additive in many foodstuffs. In order to research the genetic mechanisms which could shed light on the potential application spectrum of mould and its metabolic products, a research team from Kiel University has developed a new procedure in collaboration with colleagues from Leiden University in the Netherlands.  Read more...

Why the Japanese live longer

Nov 13, 2015

Kiel-based research team shows positive influence on life span of bioactive plant compounds in green tea and soy

A research team at the Institute of Human Nutrition and Food Science at Kiel University has discovered promising links between life expectancy and two phytochemicals - the so-called catechins and isoflavones. The underlying research by the Kiel-based scientists recently appeared in the two journals Oncotarget and The FASEB Journal. Read more...

Marine fungi contain promising anti-cancer compounds

Oct 28, 2015

A Kiel-based research team has identified fungi genes that can develop anti-cancer compounds

To date, the ocean is one of our planet's least researched habitats. Researchers suspect that the seas and oceans hold an enormous knowledge potential and are therefore searching for new substances to treat diseases here. In the EU "Marine Fungi" project, international scientists have now systematically looked for such substances specifically in fungi from the sea, with help from Kiel University and the GEOMAR Helmholtz Centre for Ocean Research Kiel. Read more...

New strategy for fighting antibiotic-resistant pathogens

Oct 16, 2015

Daily switching of antibiotics inhibits the evolution of resistance

Rapid evolution of resistance to antibiotics represents an increasingly dramatic risk for public health. In fewer than 20 years from now, antibiotic-resistant pathogens could become one of the most frequent causes of unnatural deaths. Medicine is therefore facing the particular challenge of continuing to ensure the successful treatment of bacterial infections - despite an ever-shrinking spectrum of effective antibiotics. Recent research by a group of scientists at Kiel University has now shown that there are possible ways to prolong the effectiveness of the antibiotics that are currently available. Read more...

Nematode worms hitch a ride on slugs

Jul 13, 2015

Kiel scientists expand the understanding of Caenorhabditis elegans’ natural ecology


Slugs and other invertebrates provide essential public transport for small worms including Caenorhabditis elegans in the search for food, as researchers from Kiel University have now found out. These worms are around a millimeter long and commonly found in short-lived environments, such as decomposing fruit or other rotting plant material. Read more...

Live from the Evolution Lab

Jun 05, 2015

Study on coevolution between host and pathogens sheds new light on evolutionary dynamics.

 

Every year, new cold and flu pathogens occur and problematic pathogens such as Ebola cause global alarm at regular intervals. The key to a better understanding of disease epidemics lies in the adaptability and thus in the evolution of the pathogens that cause disease. With the aid of innovative experiments in the lab, researchers in the research group Evolutionary Ecology and Genetics at the Christian Albrecht University of Kiel (CAU) have now been able to gain important insights into the evolution of pathogens. Read more...

Hidden safety switch: New findings on death receptors in cancer cells

Jun 10, 2015

Achieving a better molecular understanding of the role played in the occurrence of cancer of so-called death receptors which make the progression of pancreatic cancer in particular especially aggressive and almost always fatal – this is the goal of scientists at the Institute for Experimental Tumor Research at the Christian Albrecht University of Kiel (CAU). Read more...

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