A Search for Molecular Targets of the Rna Antitoxin Sprf1 Revealed that Rpme2 is Involved in Antibiotic Tolerance in Staphylococcus Aureus
Résumé
Slow-growing bacteria, referred as tolerant or persistent, emerge as a major health issue since they are associated with antibiotic treatment failures and relapsing infections. Among others, type I toxin-antitoxin (TA) systems have been linked to slow-growing bacteria formation. They are composed of a peptide toxin whose overexpression confers growth stasis or cell death, and of an RNA antitoxin that base-pairs with the cognate toxin mRNA to inhibit its translation. In the human pathogen Staphylococcus aureus, it was recently shown that the SprF1 antitoxin is able to bind ribosomes to inhibit global translation and promote persister cell formation. Here, we used in silico analysis and MS2-affinity purification coupled with RNA sequencing (MAPS) to expand the RNA targetome of SprF1 and better understand its role in S. aureus antibiotic adaptation. We experimentally uncovered 12 mRNAs targets interacting with SprF1 and demonstrated that SprF1 directly interacts with yidC, encoding a protein insertase, and rpmE2, encoding the ribosomal protein L31, to either decrease or increase their protein expression. Finally, we showed that rpmE2 overexpression is associated with antibiotic tolerance which could contribute to the persister phenotype mediated by SprF1. Altogether, these findings highlight that some type I RNA antitoxins behave like typical regulatory RNAs, by interacting with several targets through various regulatory motifs to participate in bacterial adaptation.
Auteurs, date et publication :
Auteurs Emeline Ostyn , Marc Hallier , Stéphane Dreano , Yoann Augagneur , Marie-Laure Pinel-Marie
Date : 2024