Intestinal bacterium allows microbiome-mediated protection against pathogens

All of the bacteria, viruses and fungi that exist in and on a multicellular organism forms its natural microbiome. The interactions between the body and these microorganisms considerably influence both the functions and the health of the host organism. Researchers assume that the microbiome plays an important role in defense against pathogens, among others.

The collaborative Research Center (CRC) 1182 “Origin and function of metaorganisms” at the University of Kiel has been studying the very complex interaction between host organizations and microorganisms for several years using various model organizations, including the Nématode Caenorhabditis Elegans.

In a recent study, CRC 1182 researchers have acquired new information on the molecular mechanisms of the microbiome which contribute to defense against pathogens. In collaboration with scientists from the Max Planck Institute for Earth’s microbiology and the University of Edinburgh, they discovered that a protective bacteria of the Pseudomonas genus, which is in the intestinal microbiome of C. Elegans, produces sphingolipids.

This result was surprising, because it was previously assumed that the production of sphingolipids was limited to only a few bacterial phyla and that the bacterial genus Pseudomonas was not known to be able to produce these specific molecules.

Researchers have discovered that pseudomonas use an alternative metabolic route for the production of sphingolipids, which differs considerably from the synthetic pathways of the sphingolipids known in other bacteria. They were also able to show that the sphingolipids produced by the bacteria of Pseudomonas play an essential role in the protection of the intestinal epithelium of the host against damage by the pathogen.

Responsible for the production of sphingolipids in the bacteria of Pseudomonas is a group of specific biosynthetic genes which forms the enzymes of this new metabolic path. Interestingly, clusters of similar genes have also been found in other intestinal bacteria associated with the host, suggesting that the ability to produce sphingolipids can be more widespread than we thought previously. This suggests that bacterial sphingolipids can play a central role in mediated microbiome protection against infection – not only in C. Elegans, but potentially also in other host organizations.

The results of the interdisciplinary study, conducted under the direction of Dr. Katja Dierking (Research group on evolutionary ecology and genetics of Kiel University), in collaboration with other Kiel research groups and national and international cooperation partners, were published in the journal in the journal Nature communications.

In 2019, the Kiel Research Group published a study in Current biology This has shown that some members of the C. Elegans microbiota protect against the infection of pathogens. “For a species of pseudomonas, we knew that it could protect the worm against infections. However, we had not yet been able to identify the substances and mechanisms involved,” said Dr. Lena Peters, a scientist of the research group on ecology and evolutionary genetics.

In a large collaboration of scientists at the same time within CRC 1182, including the teachers of Kiel Christoph Kaleta and Manuel Liebeke – and with external scientists, including Professor Helge Bode of the MPI for Earthly microbiology in Marburg and Professor Dominic Campopiano from the University of Edinburg, the genetic and metabolic field Protection against microbido inflection, the genetic and metabolic field of protection against protection against microbido inflection, was the metabolic basis of protection against protection against microbido, Metabolic Base the Against Against Infection Medico -Builder.

Using metabolic and transcriptional studies, analyzes of a single molecule and mass spectrometry approaches, researchers have made a surprising discovery: they were able to prove that the protective bacteria of the Pseudomonas genre produce sphingolipids which influence the metabolism of the sphingolipids of the worm and therefore support the protection of the host against pathogens.

“This observation is relatively new,” explains Peters, member of the CRC 1182. “Normally, bacteria use the metabolism of sphingolipids of host organisms to handle it in a targeted way to promote infections. In our case, however, we observe the opposite opposite – bacteria spingolipids actively support the protection of the host.”

Sphingolipids are fat -type molecules which are generally found in eukaryotes, where they fulfill significant structural and regulatory functions, but are rare in bacteria. In Pseudomonas, they are synthesized via an alternative metabolic route previously unknown – not as a component of primary metabolism, as is generally the case, but as a supposedly secondary metabolite.

Researchers discovered that this previously unknown metabolic path is based on a group of specific biosynthetic genes, a so-called synthase polycetide. “With our experiences, we were able to confirm that worms have survived in the presence of Pseudomonas fluorescens bacteria with this group of genes when they were infected with the pathogen Bacillus Thuringiensis”, underlines Peters, the first author of the study.

After identifying the responsible genes, scientists could confirm through other analyzes than the heap of genes code the enzymes necessary for the synthesis of sphingolipids. “It is exciting to be authors on this important revolutionary article. We are delighted that our expertise in bacterial research in sphingolid has helped discover a new role in the microbiome of Ver for these enigmatic lipids,” explains Professor Campopiano.

“The mechanism of protection against infections by B. Thuringiensis apparently works indirectly. The lipids produced by pseudomonas influence the metabolism of the sphingolid of the ver, which probably leads to an improved barrier function of the intestinal cells”, explains Peters.

When the worm is infected with B. Thuringiensis, the toxins of the pathogen create small pores in the cell membrane of the host, which facilitates the penetration of pathogens. “We assume that the metabolism of sphingolid modified by P. Fluorescens reinforces the stability and resistance of cellular membranes – and thus offers effective and indirect protection against pathogens”, continues Peters.

“Overall, the new research work is expanding our understanding of how microbial metabolites support the defend of the host against pathogens,” explains Dierking, independent group leader in the research group on ecology and evolutionary genetics.

In the long term, CRC 1182 researchers, who are also active in the priority research field of the University of Kiel, Kiel Life Science (KLS), hope that better knowledge of these fundamental mechanisms will also influence the disorders of the human intestinal microbiome, which can cause better treatment options for a variety of associated diseases.