Exploring the potential of sponges as sources of antimicrobial bacteria
Antibiotic resistance and novel ways of treating cancer tumours are two key challenges facing a diverse range of scientific disciplines. While the hunt has been on to find molecular compounds from the organisms that surround us, eyes are now turning to life beneath the waves. The EU’s BluePharmTrain project has been focussing on marine sponges as they host the richest compounds so far discovered in the oceans. Many interesting molecules have been discovered, but, so far, no suitable way to acquire significant quantities of these has been available. The tantalising potential has been hard to explore, as there is usually not even material to start clinical trials. So the project’s goal was to break through this bottleneck. Pharmacological riches beneath the waves Marine sponges harbour extremely diverse populations of microbes, and are world record holders for the production of a plethora of bioactive molecules. Previous studies, however, aiming at the growth of sponges or their associated microbes for the production of bioactive compounds to supply biological material for clinical trials, have been largely unsuccessful. “What made our project innovative was that we integrated revolutionary DNA-sequencing techniques,” says project coordinator Dr. Detmer Sipkema, based at Wageningen University in the Netherlands. As Dr. Sipkema explains, the recent conceptual and technological developments in genomics, transcriptomics and proteomics (‘omics’) have changed the way we look at genes, species and communities. These innovations also impact on other disciplines, such as ecology and biotechnology. They put ‘old problems’ in a new light and allow researchers to go far beyond previous limits. BluePharmTrain harnessed these innovative approaches to get a better idea of the physiological responses of sponges in their natural environments, including their responses to stresses such as changes in temperatures. The project was particularly keen to investigate what are currently unculturable bacterial symbionts, in a bid to set up highly tailored cultivation methods for these bacteria. “We were searching for free-living bacteria that harbour gene clusters most similar to the ones detected in sponges,” says Dr. Sipkema. Finding the sponges and ‘fixing’ them to make them stable was the simple part: the team collected the sponges and passed them to colleagues standing by with fixative. DNA and RNA were then extracted. “They all give very mixed puzzles: as if an unknown number of jigsaw puzzles was thrown together,” but by using highly sophisticated software, Dr. Sipkema and his team managed to make sense of most of the data. “This gave us insights in the genomes of the most abundant symbiotic bacteria, (which are the true producers of the majority of molecules), and allowed us to identify the host of the gene clusters encoding for the desired molecules.” New horizons for pharmacological treatments Solving these jigsaw puzzles enabled the project to find out more about the characteristics about the metabolism of the bacteria. “For example,” says Dr. Sipkema, “we now know more about the exact bacteria that are responsible for the production of terpenes with thiocyanates (which have antimicrobial properties).” The team are also clearer about what might be necessary to isolate the glycoproteins and glycolipids, present in abundant sponge symbionts. Using bioinformatic analysis the project partners managed to trace a free-living bacterium that produces a compound very similar to polytheonamide. Polytheonamides are highly cytotoxic molecules produced by, as the project discovered, symbiotic bacteria from the sponge Theonella swinhoei. Researchers managed to genetically modify this free-living bacterium so that different polytheonamide-like molecules can be produced, with different pharmacological characteristics. Benefits of the project live on Dr. Sipkema is certain that the collaboration across borders has added a positive dimension to his research. “The network really operated as a team. Very strong partnerships were set up to perform research that partners really could not have done alone. This helped us to move faster and spend the research money in a more efficient way,” he says. “The collaboration built over the lifespan of the project is still on-going and will continue for some time. I would like to capitalise on the network formed and move forward further, while profiting from the training programme set up and the high spirit of collaboration,” says Dr. Sipkema.
Keywords
BluePharmTrain, pharmacology, marine sponge, symbiosis, cancer, antimicrobial, antibiotic resistance, health, bacteria
