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Bodo Philipp – the discovery of the general principles of bacterial interaction

The way bacteria communicate and the way humans communicate is very different. While people communicate with each other acoustically and visually, current knowledge suggests that bacteria only communicate chemically using diffusible signalling substances and direct cell-cell contacts. Dr. Bodo Philipp from the University of Constance specifically focuses on ecologically relevant activities of bacteria, for example cell-cell interactions. His findings could prove effective in removing bacteria from areas where high levels of hygiene are required, thereby making it possible to prevent life-threatening bacterial infectious diseases. Dr. Bodo Philipp uses the much feared Pseudomonas aeruginosa bacteria as model organisms for his research.

Dr. Bodo Philipp © private

Traditional research sees bacteria as independent single-celled cells. However, for a few years now microbiologists have been concentrating to a greater extent on the interactions between bacteria. Little is so far known on bacterial interactions because investigations of the physiology of bacteria are traditionally almost exclusively carried out with pure bacteria cultures. Over the last few years, thousands of bacterial genomes have been sequenced and this has shown that a large number of genes (approximately 30 to 50%) code for proteins of unknown function. Since bacteria do not live in pure cultures in their natural habitats, it seems highly probable that many of these unknown genes have a function that is relevant for life in bacterial communities. Dr. Bodo Philipp uses a broad range of physiological and biochemical analyses to investigate cell-cell interactions, to identify the function of genes and to gain insights into bacterial communication mechanisms.

"In terms of practical application, our results might contribute to our understanding of how bacterial contaminations can be more effectively counteracted in hygienic areas, for example in hospitals, canteen kitchens and the food industry," said the microbiologist outlining his future goals. Philipp also envisages that basic research will open up new perspectives for white biotechnology, for example the use of bacterial cell-cell interactions for the production of useful metabolites (e.g., food supplements, pharmaceuticals) or the removal of substances (e.g., out-of-date drugs) which are hazardous to the environment.

Focus on a versatile hospital pathogen

Philipp and his team of researchers use bacteria from the genera Aeromonas, Cytophaga/Flavobacterium and Pseudomonas aeruginosa to investigate the cellular and chemical interactions between bacteria. “Pseudomonas aeruginosa bacteria can easily be genetically modified; they are extremely flexible and can adapt to a broad range of habitats where they tap diverse food sources and protect themselves against damage from toxic compounds (e.g., antibiotics, disinfectants) or predators (e.g., amoeba),” said Philipp explaining the habits of the bacteria. The bacteria’s versatility is very much based on cell-cell interactions such as aggregations, biofilm formation and chemical communication, which makes them a major threat in many areas, e.g. as opportunistic pathogens in hospitals or in drinking water and in the contamination of swimming pool water. “P. aeruginosa is a particular threat for cystic fibrosis sufferers who frequently contract P. aeruginosa lung infections,” said Dr. Bodo Philipp. Wearers of contact lenses are at risk of contracting cornea infections caused by P. aeruginosa because the bacteria survive contact lens detergents by using them as a food source and forming biofilms on the contact lens that is subsequently inserted into the eye.

Structured Pseudomonas aeruginosa colonies on an agar plate containing SDS
Structured Pseudomonas aeruginosa colonies on an agar plate containing SDS © Dr. Janosch Klebensberger

Bacteria under stress

During their initial examinations, Dr. Bodo Philipp and his team came up with the hypothesis that bacteria form cell aggregates when using toxic substances as food sources. The use of toxic substances such as tensides or solvents as food inevitably exposes the bacteria to these compounds. “We assumed that the formation of aggregates offered the bacteria protection against comprehensive cell damage,” explained the microbiologist. In order to analyse the interaction of P. aeruginosa with toxic substances, Dr. Bodo Philipp and his team of researchers used the tenside sodium dodecyl sulphate (SDS) as the model substance. SDS is a toxic compound that is degraded by bacteria in sewage plants for example. The researchers found that P. aeruginosa formed extensive cell aggregates when grown on SDS, which is a typical constituent of hygiene products such as toothpaste or shampoo. The researchers found that SDS led to the inhibition of the energy metabolism of free-living individual P. aeruginosa bacteria and as a result to the dissolution of the cells.

“However, when the cells are part of an aggregate, they are over 1000 times more resistant to SDS,” said Dr. Bodo Philipp. Philipp and his team concluded from genetic studies that SDS led to relatively mild stress in cells, which is registered by specific signalling molecules. “These signalling proteins lead to the formation of higher quantities of extracellular polymeric substances (EPS) which make the individual cells sticky, thereby causing the aggregation of the cells,” said Dr. Bodo Philipp. The researchers from Constance found that polysaccharides, DNA and a surface protein made the individual cells adhesive. They also found that this signalling cascade involved guanosine monophosphate (c-di-GMP), a common bacterial intracellular signalling molecule.

Cell aggregation as effective survival strategy

Dr. Bodo Philipp and his doctoral student Nina Jagmann investigate bacterial communication at the University of Constance. The photo shows the two researchers in the microbiology laboratory. © Dr. Bodo Philipp

"The cell aggregation induced by the exposure of the cells to SDS is a kind of pre-adaptive survival strategy. This tactic means that some of the cells of a population already aggregate when exposed to relatively mild stress," said the microbiologist from the University of Constance. This guarantees that a certain proportion of the bacterial population has a higher chance of survival when  conditions become even worse, for example when the concentration of the substance increases or when the bacteria are exposed to another toxic substance. "When exposed to SDS alone, we found that the cells did not aggregate and that longer cultivation periods led to spontaneous mutations, which led to the loss of the SDS-induced aggregation ability," said Dr. Bodo Philipp. The mutations resulted in domesticated bacteria that did not aggregate to the same degree as bacteria without the mutations.

Competition induces communication processes

In another project, Philipp and his team investigated the competition between water bacteria, i.e. Aeromonas and Cytophaga/Flavobacterium strains for polymeric substrates. They investigated how different bacteria interacted when competing for food particles, e.g. dead microalgae or the chitin carapace of shellfish. These experiments were conducted under conditions that were as similar as possible to natural conditions. The researchers used sterile filtrated water from Lake Constance. “Aeromonas bacteria are known to have a specific communication system, N-acyl-homoserine lactone (AHL)-dependent quorum sensing, which is important for biofilm formation and the production of extracellular enzymes. We therefore hypothesised that AHL-dependent quorum sensing was essential for the growth of Aeromonas bacteria on polymeric substances.” However, the different experiments showed that this was not the case. The second hypothesis was that the bacteria used as yet unknown communication mechanisms to degrade polymeric substances when cultured under natural conditions, i.e. conditions with limited nutrients.

Bodo Philipp and his team were clear about how the sequencing of the experiments was to be carried out. “In general, we investigate certain cell-cell interactions, for example the SDS-induced aggregation or biofilm formation of bacterially degraded dead algae in the laboratory, physiologically and then biochemically. Based on these findings, we then create mutants that no longer interact. This helps us to identify the genes that are specifically involved in such interactions,” said Philipp. Besides many traditional microbiological and chemical-analytical techniques (e.g., HPLC) and molecular genetic methods (PCR, DNA chips), we also use fluorescence microscopy and confocal laser scanning microscopy to investigate the structure of aggregates and biofilms.

Cooperation with industry might potentially lead to products

Philipp would like to work with industrial partners, particularly companies focusing on white biotechnology. “Such partnerships would enable us to focus on the investigation of whether the induction of cell aggregation has any advantage for some fermentation processes or whether cell-cell interactions between different bacteria could be used for multi-tier fermentation processes,” said Dr. Bodo Philipp. The researcher also envisages that further cooperations with manufacturers of liquid hygiene products would enable him to analyse, and potentially prevent, the growth of bacteria on such products. Dr. Bodo Philipp also envisages the possibility of working with industrial companies in order to investigate metabolic paths that lead to the degradation of stable organic compounds such as steroids and aromatic compounds. Some years ago, the team of researchers worked with a team from BASF AG on a project dealing with the predictability of the biological degradability of organic compounds. “Our group has the expertise, willingness and flexibility to work with industrial partners who would like to invest in a basic research project. We would very much appreciate financial support in order to be able to carry out expensive analyses (e.g., DNA chips) or pay for a doctoral student post,” explains the microbiologist.

Apart from seeking out contacts in industry, Philipp and his team also intend to focus on bacterial research. “We hope to concentrate on the discovery of general principles of bacterial interactions such as the identification of friends and foes and on the combination of metabolic physiology and cell-cell interactions. Philipp and his team are also planning to carry out experiments to investigate new metabolic pathways, e.g. for micropollutants (e.g., drugs, softening agents) that are difficult to degrade in sewage plants and thus accumulate in the environment.

Background: 

Bodo Philipp studied biology at the University of Osnabrück with a major focus on microbiology, genetics, biophysics and ornithology. After his degree at the Institute of Biotechnology at the Research Centre Jülich and his doctorate in 1999 on the degradation of phenolic compounds by anaerobic bacteria at the University of Constance, Philipp spent one year as a post-doctoral student during which he worked with BASF AG and computer scientists in order to assess the predictability of biological degradability. In 2000, Philipp moved to England to start investigations at the University of Nottingham on bacterial communication before returning to the University of Constance in 2001. He habilitated in the field of microbiology and microbiological ecology in 2008.

Further information:

Dr. Bodo Philipp
University of Constance
Faculty of Biology
Microbial Ecology
Tel.: +49 (0)7531 / 88-4541
E-mail: bodo.philipp@uni-konstanz.de

Website address: https://www.biooekonomie-bw.de/en/articles/news/bodo-philipp-the-discovery-of-the-general-principles-of-bacterial-interaction