Manuela Fuchs    email
Research Center for Infectious Diseases

Supervisor:
Dr. Franziska Faber (Würzburg)
Promotion Committee:
Dr. Franziska Faber (Würzburg)
Jun.
Prof. Dr. Alexander J. Westermann (Würzburg)
Dr. Meina Neumann-Schaal
(Braunschweig)

Global discovery of Hfq associated RNAs in the enteric pathogen Clostridioides difficile

 

Clostridioides difficile (C. difficile) is a Gram-positive obligate anaerobic bacterium, constituting the leading cause of nosocomial diarrhoea. C. difficile infection is facilitated by antimicrobial therapy-mediated disruption of the colonic microflora, leading to germination of residing C. difficile spores. Following germination and proliferation expression of the major virulence factors, large clostridial toxin TcdA and TcdB causes alterations in the actin cytoskeleton of intestinal epithelial cells, resulting in diarrhoea, inflammation and tissue necrosis. Although numerous studies have significantly expanded our knowledge about C. difficile infection mechanisms, many aspects including those involved in regulation of virulence and colonization factors remain poorly understood.

Recent data published by Soutourina et al. suggest the importance of RNA-based mechanisms for the control of gene expression in C. difficile, as shown for many other pathogenic bacteria.[1]  In Gram-negative species the function of many sRNAs is facilitated by the RNA chaperon Hfq that increases their intracellular half-life and stabilizes the interactions between sRNAs and their target RNAs. Although Hfq and its RNA binding partners have been studied expensively in many Gram-negative bacteria, the role of Hfq in Gram-positive bacteria remains less defined. Recent phenotypic and transcriptomic analysis of an Hfq-depleted C. difficile strain provided first insights into the function of Hfq in C. difficile.[2] However a global study of Hfq associated RNAs remains to be performed. Therefore, my PhD project aims to identify global Hfq interaction partners using high throughput RNA-sequencing technologies such as CLIP-seq and RIL-seq.

 

[1] A. Soutourina et al., “Genome-wide identification of regulatory RNAs in the human pathogen Clostridium difficile,” PLoS Genet., 2013.

[2] P. Boudry et al., “Pleiotropic role of the RNA chaperone protein Hfq in the human pathogen Clostridium difficile,” J. Bacteriol., 2014.