Research

Topics

We focus on bacteria that form serious health threats, such as multidrug resistant microorganisms, as well as bacteria that have potential health beneficial effects.

Key to our research over the past 20 years is the anaerobic Gram-positive enteropathogen Clostridioides difficile. Motivated by epidemiological and diagnostic challenges in the early 2000's during outbreaks of C. difficile, our work has since then expanded into other, more fundamental, aspects as well. Some of our favorite topics include antimicrobials and antimicrobial resistance, stress responses, plasmids, proteolysis, post-translational modifications, and DNA replication. 

In addition to C. difficile, we also work on other organisms, such as Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Escherichia coli and Ruminococcus gnavus, for instance.  We have a particular interest in differences and similarities between C. difficile and these other organisms, and how organisms interact in the context of complex communities, such as the gut microbiome.

Most recently, we have been developing controlled human colonization and infection models for C. difficile.

Techniques

Facilities

Laboratories

Our laboratories are suitable to work with genetically modified organisms belonging to safety levels up to BSL-2 (in the Dutch system: ML-1 and ML-2 classification).

As a main focus of our lab is working with anaerobic bacteria, we have multiple anaerobic cabinets at each safety level: Whitley A35 (Dr. Who), Whitley A135 GMP (Turdis), Whitley A55 HEPA (Whitley Houston),  Whitley VA1000 (Big Don) and a Baker Ruskinn Concept 1000 (Ma Baker). As you can see, we like to call these by their given names.

Besides much of the routine equipment for a molecular biology lab (PCR machines, blotting apparatus etc), we also have for instance an automated DNA extraction platform (Promega Maxwell RSC48), multimode microplate reader (Promega GloMax), spiral plater (Whitley Wasp Touch), colony counter (Interscience SCAN500), FPLC system (Akta Pure) and DM6B fluorescence microscope (Leica) at our disposal.

LUMC Facilities

• Center for Proteomics and Metabolomics (CPM): as our long-term collaborator (see below), CPM provides state-of-the-art infrastructure and expertise for our proteomics work 

• Leiden Genome Technology Center (LGTC): LGTC provides next generation sequencing service, and is our go-to partner in particular for long-read sequencing (Pacific Biosciences)

• Protein Facility: offers access to a wide range of protein purification and characterization platforms

• Light and electron microscopy Facility: we work with this facility for some of our structural studies

• Center for Cell and Gene Therapy (CCG): provides expertise that is instrumental for the production and distribution of our challenge material for human interventions

• Netherlands Center for Nanoscopy (NeCEN): if we need the best possible cryo-EM microscopes, we have this Center just around the corner

Center for Microbiota Analysis and Therapeutics

Collaborations

We work together with many local, national and international partners. Some of these are highlighted below.

• Paul Hensbergen and his team at CPM have been instrumental in joint studies on protein abundance, proteolysis and post-translational modifications of C. difficile and other bacteria. We have been working together for over 10 years and regularly jointly supervise students. Some of the highlights of this collaboration include the identification of the first characterized Pro-Pro Endopeptidase, PPEP-1, and the elucidation of the pathway for the post-translational modification of flagellin.

• Nathaniel Martin 's group is developing new drugs for the treatment of problematic bacteria. Our current collaboration focuses on the novel lipoglycopeptide antibiotic EVG7 in treatment of S.aureus and C. difficile infections.

• The controlled human colonization and infection model for C. difficile is a close collaboration with the group of Meta Roestenberg (L-CHIC, InfectNL).

• Together with the team of Marcela Krůtová we identify and characterize novel antimicrobial resistance mechanisms. 

• The activities as an expertise center for C. difficile infections benefit from long standing collaborations with the HCAI group in Leeds, UK (Mark Wilcox, Jane Freeman) as well as the Anaerobic Reference Unit (UKARU) in Cardiff, UK (Trefor Morris)

• Our group also works together with industrial partners, such as Vedanta Biosciences and Acurx Pharmaceuticals.