RNA Quality Control Enables Antibiotic Tolerance.

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Antibiotic resistance in complex host environments is not fully understood.
• Adaptation mechanisms of Streptococcus pneumoniae under selective pressures require further investigation.

Purpose of the Study:

• To elucidate the adaptive strategies of Streptococcus pneumoniae under antibiotic and immune stress.
• To identify genetic mutations and molecular mechanisms conferring antibiotic tolerance and accelerated recovery.

Main Methods:

• Experimental evolution of Streptococcus pneumoniae under diverse antibiotic and immune conditions.
• Whole-genome sequencing and single-cell transcriptomics to analyze adaptive mutations and cellular responses.
• Investigating the role of RNase Y (rny) in antibiotic tolerance and RNA homeostasis.

Main Results:

• Convergent mutations in the rny gene were identified, conferring broad-spectrum antibiotic tolerance and faster recovery.
• Antibiotic stress induces transcriptional collapse, a loss of RNA quantity and integrity.
• rny mutants employ a bet-hedging strategy, with a resilient subpopulation maintaining transcription and a quiescent majority degrading RNA to preserve fidelity.
• A prioritized transcriptional ribosomal reboot facilitates accelerated recovery upon stress removal.

Conclusions:

• RNA turnover, regulated by RNase Y, is a critical master regulator for bacterial survival under combined antibiotic and immune pressures.
• The identified bet-hedging strategy and RNA preservation mechanisms offer novel insights into antibiotic resistance and bacterial adaptation.
• Targeting RNA turnover pathways could be a potential strategy to combat antibiotic resistance in complex infections.