PhD Graduate Van Groesen: ‘Nothing is too crazy to try.’
In a world where bacteria are increasingly resistant to antibiotics, Emma van Groesen set out to find a solution. This month she obtained her PhD, after four years of research into new variants of the antibiotic vancomycin. With success.
‘Vancomycin is currently used as a last resort against bacteria that are resistant to many other antibiotics, such as MRSA. But even to vancomycin, bacteria now become immune,' says Van Groesen. 'So to avoid pathogenic bacteria that will soon be unstoppable, we need to find something new.’
Van Groesen worked in Nathaniel Martin's lab (Institute of Biology Leiden) on making new antibiotics. In doing so, she used the existing vancomycin, but added groups of molecules to the structure of the drug. In this way, the groups can each ‘attack’ a different part of the bacteria, which the pathogens are unable to combat.
‘During my PhD, I made several antibiotics by using this method. These worked on different types of bacteria: On so-called gram-positive bacteria, such as MRSA, and gram-negative bacteria,' Groesen says enthusiastically. These bacteria differ because of the composition of their outer layer, which is harder to break through in gram-negative bacteria. ‘But still my modified vancomycin gets through that, so a bacterium actually collapses like a flat tyre and dies.’
Experimenting in all directions
Van Groesen's PhD has now been completed. Her most promising antibiotic has advanced to mouse studies, the next stage in antibiotic development. This vancomycin appears to be up to a thousand times more active than the original vancomycin against gram-positive bacteria.
‘It is quite extraordinary. You add two separate components together, and it is very cool that they turn out to reinforce each other,’ the researcher says. It is one of the reasons she found the experimental part of the PhD most enjoyable. ‘You can go in many directions. Nothing is too crazy to try. Sometimes that ends up in nothing, and I can understand why that gets turned down in other workplaces faster. Now I was given the opportunity to investigate exactly how something was put together and was able to make a success of it.’
Planning extra well
Yet there were also difficult elements during the four years, especially working around Covid-19. ‘I didn't find it difficult to set myself tasks and stay busy. But as a researcher, we had to plan experiments extra well.’ Laughing, she adds, ‘Although by now I have almost forgotten that we had to take that into account!’
van Groesen, E., Slingerland, C. J., Innocenti, P., Mihajlovic, M., Masereeuw, R., & Martin, N. I. (2021). Vancomyxins: Vancomycin-polymyxin nonapeptide conjugates that retain anti-Gram-positive activity with enhanced potency against Gram-negative strains. ACS infectious diseases, 7(9), 2746-2754.
van Groesen, E., Innocenti, P., & Martin, N. I. (2022). Recent advances in the development of semisynthetic glycopeptide antibiotics: 2014–2022. ACS Infectious Diseases, 8(8), 1381-1407.