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Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
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An ADP-ribosyltransferase toxin kills bacterial cells by modifying structured non-coding RNAs
Nathan P Bullen1, David Sychantha1, Stephanie S Thang1
1Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Molecular Cell
|September 7, 2022
Summary
Researchers discovered RhsP2, a novel ADP-ribosyltransferase (ART) toxin used by Pseudomonas aeruginosa. This toxin targets double-stranded RNA, inhibiting translation and tRNA processing, revealing a new bacterial antagonism mechanism.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- ADP-ribosyltransferases (ARTs) are known bacterial virulence factors.
- Traditionally, ART toxins target and modify host proteins to disrupt cellular functions.
- ARTs also play roles in antibiotic inactivation and DNA repair.
Purpose of the Study:
- To identify and characterize novel bacterial toxins.
- To investigate the mechanism of bacterial antagonism mediated by type VI secretion systems.
- To uncover new enzymatic activities of ARTs.
Main Methods:
- Structural analysis of the RhsP2 toxin.
- Biochemical assays to determine substrate specificity.
- Investigation of cellular targets and downstream effects in Pseudomonas aeruginosa.
Main Results:
- Discovery of RhsP2, an ART toxin delivered by a type VI secretion system.
- RhsP2 exhibits a novel activity: ADP-ribosylation of double-stranded RNA.
- Identified targets include tRNA and ribonuclease P, leading to translation inhibition and cell death.
Conclusions:
- RhsP2 represents a previously undescribed mechanism of bacterial antagonism.
- ART enzymes can catalyze unprecedented RNA-modifying activities.
- This discovery expands the known functions of ARTs beyond protein modification.
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