dr. Wiep Klaas Smits

Associate professor
w.k.smits[at]lumc.nl orcid orcid.org/0000-0002-7409-2847
dr.

Research

My research focuses on pathogenic bacteria, in particular Clostridioides difficile and Staphylococcus aureus. I am also interested exploring the use of live biotherapeutic products, including anaerobic bacteria, as possible interventions.

Within the Center for Microbiota Analyses and Therapeutics (CMAT), we study all aspects of the complex role of the microbiota in health and disease.

For C. difficile I am closely involved with the Dutch National Expertise Center for C. difficile infections, a collaboration between the LUMC and the Center of Infectious Disease Control of the National Institute for Public Health and the Environment. A major focus in my research is the characterization of the multi-protein machinery responsible for DNA replication, and the response of bacteria to environmental stresses (including sub-inhibitory and inhibitory concentrations of antimicrobial compounds). In recent years, my team has for instance identified novel mechanisms of antimicrobial resistance and uncovered a role for plasmids in C. difficile.

Our work is highly cross-displinary (genetics, molecular biology, biochemistry) and increasingly involves translational aspects. Most recently, I have become interested in the use of a controlled human colonization and infection models for the study of bacterial infectious diseases.

My research is supported by for instance grants from the European Union, the Dutch Research Council (NWO), Health~Holland, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), and Leiden University Fund (LUF).

Curriculum vitae

I studied Biology at the Faculty of Mathematics and Natural Sciences, University of Groningen (Groningen, The Netherlands). During my PhD at the same institute I studied bacterial gene regulation in Bacillus subtilis in the laboratory of prof. O.P. Kuipers.

Following my PhD I performed postdoctoral research at the Massachusetts Institute of Technology (Cambridge MA, USA) under the guidance of prof. A.D. Grossman. Here, I studied DNA replication of Bacillus subtilis using biochemical and omics techniques.

After my postdoctoral research, I joined the Leiden University Medical Center, in the group of Prof. E.J. Kuijper. Here, I developed my own line of research focusing on the Gram-positive enteropathogen Clostridioides difficile.

Currently, I head the research group Experimental Bacteriology and the Center of Microbiome Analyses and Therapeutics.

I am a member of the steering committee of the International Conference on the Molecular Biology and Pathogenesis of Clostridia, and Education Officer for the ESCMID Study Group on Clostridioides difficile.

Links

Google Scholar

Lab website

Bluesky

LinkedIn

Publications

  • A unique inhibitor conformation selectively targets the DNA polymerase PolC of Gram-positive priority pathogens.

    Urem M, Friggen AH, Musch N, Silverman MH, Swain CJ, Barbachyn MR, Mortin LI, Yu X, DeLuccia RJ, Lamers MH, Smits WK.

    Nat Commun. 2025 Nov 6;16(1):9784. doi: 10.1038/s41467-025-65324-8.

  • Clostridioides difficile should be considered a bacterial priority pathogen.

    Smits WK, Garey KW, Riley TV, Han YW, Young VB, Heritage J, Lillis CJ, Lyras D, Rupnik M, Johnson S.

    Lancet Microbe. 2025 Nov;6(11):101184. doi: 10.1016/j.lanmic.2025.101184. Epub 2025 Jun 26.

  • How to develop a controlled human infection model for Clostridioides difficile.

    Hensen ADO, Vehreschild MJGT, Gerding DN, Krut O, Chen W, Young VB, Tzipori S, Solbach P, Gibani MM, Chiu C, de Keersmaecker SCJ, Dasyam D, Morel S, Devaster JM, Corti N, Kuijper EJ, Roestenberg M, Smits WK.

    Clin Microbiol Infect. 2025 Mar;31(3):373-379. doi: 10.1016/j.cmi.2024.08.025. Epub 2024 Aug 29.

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