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It is hard not to get excited when talking with Jos van Strijp, a Professor of Microbiology at the ľ�ϸ���Ӱ�� Medical Center Utrecht and Jeroen den Hertog, a Professor of Molecular Development Zoology who is employed at the Hubrecht Institute of the Royal Netherlands Academy of Arts and Sciences. They are using the Seed Money allocated to them by Utrecht ľ�ϸ���Ӱ�� to research exactly how MRSA bacteria (hospital bacteria) cause infections at a molecular level. They are building a model based on this research that, in due course, could be very useful in the fight against festering infections. Unfortunately, this is a very real threat we are facing today.

It is the perfect combination: Van Strijp supplies the bacteria and the expertise about cell mutations , and Den Hertog  tests them on zebra fish. Both men enjoy sound international reputations on account of their knowledge and research. They previously met occasionally in the field of research into fungi, but this is the first time they are actually conducting such a large-scale research project together. Den Hertog says, enthusiastically, “This initiative came from Jos van Strijp. He suggested it and convinced me of the possibilities.”

Virulence factors

Van Strijp explains: “The bacterium we are working with, MRSA (hospital bacterium), targets people specifically and is impossible to test on other animals such as mice. This is because you will have to give mice more than 500 million bacteria at once, which is not really comparable to humans. Relatively speaking, it is just as difficult with zebra fish, which involves 1500 bacteria. However, it is easier to modify these animals at a molecular level to make them more similar to people and thus more susceptible to this type of infection.” Den Hertog adds, “Obviously, we follow all the rules. Zebra fish are animals that live in groups, so we keep a number of them together in a tank. They live in water kept at a temperature of 28 degrees Celsius.” Van Strijp's eyes begin to shine: “If it works, we can build a better model for Staphylococcus infections than we have now. We know all the virulence factors that cause harm. Three of the factors target the same receptor. That is where we will start. We aim to do five in due course, which will make them susceptible to ten virulence factors.”

Transparent

The results are impressive. “We are now testing one receptor first. Jeroen knows how to incorporate a certain mutation in a cell without disrupting it. With zebra fish, you can also see very clearly what is happening - after all, they are transparent in early life. We can study them under a microscope while they are alive. The aim is to first make them susceptible so that we can eventually see which antibiotics are effective. We add a dye to the cells and can actually watch them travel through the fish.”

Both researchers emphasise the importance of the exercise. Van Strijp says, “The aim is to eventually find out how we can contain certain bacteria. It is something we are hardly aware of nowadays, but it is perfectly possible that one day we will be facing immune diseases we are unable to control. And I am not talking about the distant future, unfortunately. The WHO recently stated that there are two major threats to human life on earth - the warmer climate and resistance to antibiotics. They are right.”

It seems barely conceivable that this research on zebra fish could have such a significant impact. Nonetheless, Van Strijp believes this is the best method: “The difficult thing is to explain the simple beginnings of our work. We know a lot about the MRSA infection, such as which part of the receptor is responsible in the case of an optimal infection. That is precisely the part of the zebra fish that we are testing, thereby making them susceptible to MRSA bacteria. Because of technological developments, we are now able to see exactly what happens inside a cell. Once we have completed this research, we can add some complexity and see if the model holds up.”

EU application

The Seed Money does not seem much for this type of research, not even to finance its initial stages. “This funding at least helped us on our way,” Van Strijp says. “I am currently in the process of following it up with an application to the EU. It would be nice if we had made a little more progress, but at least we already have some results to demonstrate. We now have a post-doctoral researcher; if our application is approved, we will be able to have more people working on the project.” Den Hertog says, “In our field, it is about trying to make progress as quickly as possible.”

Two leading institutes within walking distance of each other

For the researchers, the situation in Utrecht is ideal. Den Hertog says, “The nice thing is that we have two leading institutes within walking distance of each other, which also work together. We cannot do this ourselves, because no animals are allowed in the UMCU, and we definitely do not want any pathogenic bacteria in the Hubrecht Institute. If you were to carry out this research with an international partner, it would take one hundred times as long. The researchers need to be in contact on a daily basis and work closely together. This working partnership is of great value in itself.”

Text: Youetta Visser