Funded in the Leibniz Competition: “meta-CDI”

What makes the intestinal pathogen C. difficile so successful – and which factors contribute to the varying virulence of divergent phylogenetic lineages in C. difficile? 

Clostridioides difficile is regarded as the main cause of antibiotic-related intestinal inflammation. While most cases are mild, the number of severe or even life-threatening cases has risen over the past twenty years. These infections, usually caused by antibiotic use, are very hard to treat and often recur. The reasons behind the pathogen’s success are still not well understood.

C. difficile possesses the genetic potential to produce various antibiotics and toxins that may disrupt the intestinal flora thereby facilitating colonization and toxin production by the pathogen. This project aims to uncover these previously overlooked substances and clarify their role in gut microbial interactions using molecular biology and analytical chemistry tools. The “meta-CDI” project aims to identify these previously overlooked substances and clarify their role in microbial interactions in the gut using molecular biology and chemical analysis tools.

Who is involved?

meta-CDI brings together research groups from two leading research institutions in Jena and Würzburg, who share a history of scientific excellence in natural product research, microbiology, and infection biology.

Franziska Faber is a professor at the Institute for Hygiene and Microbiology, of the JMU in Würzburg. Work in her group focuses on the contribution of regulatory RNAs to the pathogenesis of Clostridioides difficile. They combine advanced RNA-sequencing based approaches with biochemical, genetic and microbiology techniques to dissect the regulatory mechanism governing virulence gene expression. They have generated a genetic toolbox and several global datasets that are available for the wider research community through interactive web browsers. Furthermore, her group aims to understand how virulence regulation in C. difficile is shaped by specialized metabolites, both produced by the host/microbiota and the pathogen itself. Here, they employ in vitro co-cultivation approaches as well as human organoid-based (co-)infection models to study these processes in the context of host-microbe interactions. 

Christian Hertweck is Head of the Department of Biomolecular Chemistry at the Leibniz Institute for Natural Product Research and Infection Biology and a Full Professor at Friedrich Schiller University Jena. His department's research focuses on identifying and characterizing drug candidates and virulence factors of microbes, especially those from less-studied bacterial lineages. By combining chemical and biological methods, his group explores new ways to discover bioactive compounds, determine molecular structures and biosynthetic pathways, and study biological functions.

Background: The Leibniz Competition

The “meta-CDI” project is being funded in the Leibniz Competition for a period of three years and will support one postdoctoral and three PhD positions. The competition supports the achievement of the Leibniz Association’s strategic goals as part of the Pact for Research and Innovation. The project approvals enable research at the highest level. The Leibniz Association is funding a total of 27 projects in the 2025 selection round.

More information can be found here: https://www.leibniz-gemeinschaft.de/en/research/leibniz-competition