EN | DE

A closer look at intestinal bacteria

How do bacteria defend themselves against attacks? This is the central question of a new research project led by Würzburg microbiologist Franziska Faber and supported by the Boehringer Ingelheim Foundation.

During a bacterial infection, the responsible pathogens are usually exposed to many attacks: Immune cells aim to eliminate the invaders, while competing bacteria, sensing the disturbance, may develop their own defense strategies. And of course, antibiotics and other medications also put pressure on the intruders.

However, many bacterial strains are far from defenseless. They possess various survival and adaptation strategies, such as forming biofilms, producing endospores, or transforming into “persisters” —cells that grow very slowly or not at all, thereby evading most antibiotics.

600,000 euros from the Boehringer Ingelheim Foundation

The triggers that activate certain survival strategies, such as spore formation, and the molecular mechanisms underlying these processes remain poorly understood.

A new research project at the Julius-Maximilians-Universität Würzburg (JMU) aims to change this. The project, led by Franziska Faber, Professor of Microbial Interactions at JMU’s Institute of Hygiene and Microbiology and associated group leader at the Helmholtz Institute Würzburg (HIRI), is supported with 600,000 euros as part of the Boehringer Ingelheim Foundation’s Rise-up! program.

While numerous studies have explored changes in gene expression linked to bacterial survival strategies, they often focus on large bacterial populations. As a result, these findings only provide “average” values across thousands or millions of cells. This is problematic because many survival strategies occur in only a small subset of a bacterial population. “The specific cellular states that lead to different bacterial stress responses are still largely unknown,” says Franziska Faber, explaining the background of her project.

Spotlight on Clostridioides difficile

In contrast, Faber’s research aims to analyze individual cells more closely, with a focus on Clostridioides difficile. These bacteria are a leading cause of diarrhea following antibiotic treatments.  Their ability to form antibiotic-resistant spores contributes to high relapse rates and increased mortality.

Faber is investigating which cellular states are associated with the onset of spore formation, what signals trigger this process, and how spore formation is regulated in conjunction with other defense techniques, such as toxin production.

In her three-year research project, the scientist is integrating techniques such as single-cell RNA sequencing and fluorescence in situ hybridization with genetic, biochemical, and microbiological approaches. Through this comprehensive strategy, she aims to obtain a precise understanding of the molecular mechanisms that make C. difficile so successful in combating invaders.

Ultimately, Faber hopes her findings will connect specific bacterial cell types to distinct “virulence phenotypes” on a molecular level. With this knowledge, it will be possible to identify the specific circumstances associated with, for example, spore formation during C. difficile colonization in order to develop targeted interventions.

The Rise-up! program

The Rise up! program is aimed at outstanding and exceptionally creative basic scientists in biology, chemistry, and medicine who have accepted their first appointment to an associate professorship at a German university. It supports especially innovative research projects that may have a lasting impact on their field.

About the foundation

The Boehringer Ingelheim Foundation is an independent, non-profit foundation that promotes medical, biological, chemical, and pharmaceutical science. It was established in 1977 by Hubertus Liebrecht, a member of the family of shareholders of the Boehringer Ingelheim company. Through its various activities, funding programs, and scientific awards, the foundation strives to create the freedom and thus excellent research conditions for scientists to achieve outstanding results in basic research.

 

Text: JMU Press office (adapted and translated by HIRI)
Image: HZI / Manfred Rohde