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Spying on molecular structures
Spying on molecular structures
Time for a celebration! Our manuscript "A unique inhibitor conformation selectively targets the DNA polymerase PolC of Gram-positive priority pathogens" came out in Nature Communications. We are super excited about this work, that is the result of many years of hard work by our team.
The manuscript looks at a new class of antimicrobials, one of which (ibezapolstat) is entering Phase 3 clinical trials for the treatment of C. difficile infection. It seems therefore fitting that this paper is published in C. difficile Awareness Month (an initiative of the Peggy Lillis Foundation). But the broader outlook is that these drugs can be developed for other important Gram-positive pathogens as well.
In a nut shell, we determined the structure of a complex of the antimicrobial, its target and DNA. This gives us important information about how the antimicrobials from this class work, and also what mutations cause the bacterium to be less susceptible to the drugs and why.
Read more about this work here:
November 10, 2025
Wiep Klaas Smits
Artist's impression of the interaction between PolC, DNA and ACX-801, against a background of E. faecium cells. Credit: Ella Maru Studio
LUMC's POLSTOP team (from left to right): Meindert Lamers, Wiep Klaas Smits, Nina Musch, Annemieke Friggen, and Mia Urem.
Credit: Daniel Melton
2025
2025
C. difficile should be considered a Bacterial Priority Pathogen
C. difficile should be considered a Bacterial Priority Pathogen
Every few years, the World Health Organisation (WHO) puts out a list of Bacterial Priority Pathogens, which is intended “to guide research, development and strategies”. In reality, though, this list is also used by funding agencies to decide on research on which organism will be eligible for their resources. Great if your organisms makes the list, not so great if you don’t.
The 2024 list disappointingly did not include Clostridioides difficile. At the 8th International C. difficile Symposium (September 17-19, 2024) I took part in a panel discussion on this topic. Not surprisingly, the C. difficile field present there felt that the organism SHOULD have been on there. A WHO representative, having heard the panel discussion, indicated that if one wants to make the list, this requires effort from the community.
We took this to heart. Already at the meeting, I suggested we put together an Opinion piece to present the arguments why C. difficile is an organism that should be prioritized based on the WHO criteria. Together with the other panelists, we wrote a manuscript that was recently published in the journal Anaerobe.
We felt, however, that the message we wanted to convey went beyond the C. difficile field. After all, research on many organisms absent from the list could suffer consequences which ultimately impact patient safety. To highlight this, we prepared a Correspondence that is now published in Lancet Microbe, in response to a news item in that journal about the WHO list. I am particularly proud of the fact that - to highlight the fact that our message is broadly supported - we involved not only researchers and clinicians, but also patient/carer representatives and academic societies.
I hope that our efforts not only resound within the C. difficile community, but also act as a call-to-action for others to make sure that we continue with groundbreaking research to ultimately improve clinical care, whether or not “we made it on the list”.
June 26, 2025
Wiep Klaas Smits
New website
New website
Welcome to our new lab website. This is a work in progress. The data on this site is not yet complete, but we are working on it ;)
June 16, 2025
Wiep Klaas Smits
Page updated
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