Genetic technique reveals pathogens much more accurately PhD student Jordy Coolen provides insight into spread of infections

Jordy Coolen and his team developed a genetic technique to map pathogens very accurately, both in humans and in, for example, wastewater. Several Dutch labs searching for variants of the coronavirus are now using the technique. But it is actually suitable for all pathogens. 'This will increasingly replace the old methods for analyzing infections.'

Pathogen outbreaks, we hear about them more and more. SARS-CoV-2, monkeypox and recently Candida auris. Managing such outbreaks requires knowledge: how does it spread, where do new and perhaps dangerous variants emerge, and when does drug resistance develop? Analysis of the genetic material of pathogens by sequencing provides that insight. It shows where pathogens come from and what their specific properties are, such as pathogenic potential and susceptibility to drugs.

But although the price of sequencing has dropped significantly in recent years, it is still an expensive technique for wide application. Especially when looking for tiny amounts of a pathogen's DNA in a sea of contamination, such as in wastewater. Jordy Coolen, a PhD student at Radboud university medical center, came up with several solutions to implement sequencing in routine care. His work also included a collaboration with the company NimaGen. With relatively simple steps and lower costs, he was able to very sensitively analyze the genome of microorganisms.

Variants

Sequencing technology is becoming increasingly sensitive, faster and more accurate. It detects variants of coronavirus and other microorganisms much more easily than the old techniques. During the corona pandemic, therefore, the technique Coolen helped to develop has been used nationwide in germ surveillance, for which laboratories determine which variants circulate on behalf of the Ministry of Health, Welfare and Sport. ‘I estimate that 70% of all labs in the Netherlands use the technique on samples from the GGD and hospitals’, Coolen says.

Promotor and medical microbiologist Heiman Wertheim thinks sequencing will increasingly replace traditional methods of analysis of infections. ‘We have long been analyzing human DNA in diseases such as cancer, but need to do this also more often in infections. I hope we will be using this much more in microbiological diagnostics, because it gives so much more information than the older techniques. For example, if we know that a pathogen is resistant to a certain drug, we can choose another drug. This method has already been established for infection prevention. Sequencing is actually the modern microscope for microbiology laboratories.’

Because of its sensitivity, the technique lends itself to many applications. ‘For example, in the Netherlands we monitor coronavirus in hospitals and wastewater, but we can easily expand that to other pathogens’, Coolen says. ‘In addition, we already apply this technique weekly in clinical diagnostics to detect so-called non-tuberculosis mycobacteria, a growing medical problem. For this we are a reference lab in the Radboudumc.’

More information about this thesis defense

Thesis defense on March 31, 2023 at 10.30 am by Jordy P.M. Coolen. Title dissertation: Next-generation molecular diagnostics: Role in outbreaks, drug management and routine molecular diagnostics (available online after March 31). Supervisors: Prof. Dr. H.F.L. Wertheim and Prof. Dr. M.A. Huijnen, co-supervisors: Dr. W.J.G. Melchers and Dr. A.J.H. Cremers. The defense can be followed via this livestream.

PhD student Jordy Coolen

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