Shigella secreted factors and host cell RNA metabolism
Investigator: Dr. Patryk Ngondo
Shigella is an enterobacterial human pathogen that undergoes an infectious cycle involving an intracellular lifestyle. Similar to numerous other bacteria, it has evolved the ability to hijack host cellular processes and to dampen host defense mechanisms to its advantage using secreted virulence factors. While these effectors have mainly been studied for their influence on host proteins, their potential to target host nucleic acids remains largely unexplored. It is now well established that bacteria, including Shigella, have evolved an impressive toolset to regulate their own RNAs using both proteins and RNAs molecules. It is therefore conceivable that Shigella secreted proteins may also influence host RNA metabolism leading to alterations in RNA synthesis, stability, structure, localization, or modification that favor the pathogen. Hence, our objective is to identify factors affecting host RNAs metabolism during Shigella’s intracellular lifestyle in human cell types relevant for the pathogenesis: epithelial cells, macrophages and neutrophils. Our research approach integrates traditional molecular biology techniques with state-of-the-art methodologies such as SLAM-seq and BioID. We aim to achieve the following goals:
- Dissect host genes or gene networks perturbed by Shigella during its intracellular lifestyle.
- Unravel Shigella virulence factors targeting host RNA metabolism and investigate underlying molecular mechanisms.
- Determine the broader implications of the modulation of host RNA metabolism in shaping the intricate interplay between Shigella and its host cells.
Fluorescence microscopy image of HCT-8 colon cells infected with Shigella flexneri (green)
Transcriptome changes in HCT-8 cells invaded by Shigella flexneri, analyzed by RNA-seq.
Funding sources: ANR JCJC grant and IdEx University of Strasbourg.