RNA quality control enables antibiotic tolerance

Area of Science:

• Microbiology
• Immunology
• Genetics

Background:

• Antibiotic resistance is a major global health threat.
• Pathogen adaptation mechanisms are diverse and influenced by host environments.

Purpose of the Study:

• To investigate how host immune states impact the adaptive evolution of Streptococcus pneumoniae under antibiotic pressure.
• To identify specific genetic and molecular strategies employed by bacteria to survive combined antibiotic and immune challenges.

Main Methods:

• Experimental evolution of Streptococcus pneumoniae in mouse models with varying immune states (neutrophil-replete vs. depleted).
• Genomic and transcriptomic analyses to identify mutations and adaptive pathways.
• Phenotypic characterization of evolved strains under stress conditions.

Main Results:

• Canonical antibiotic resistance mutations were costly and rarely emerged.
• Neutrophil-replete environments favored immune-evasive mutations (nicotinamidase).
• General antibiotic stress led to convergent mutations in rny (RNase Y), enabling a bet-hedging strategy involving RNA degradation and transcriptional resilience.
• rny mutants exhibited enhanced survival against antibiotic-induced transcriptional collapse and facilitated rapid recovery upon stress removal.

Conclusions:

• Host immune status significantly shapes bacterial adaptive strategies to antibiotics.
• RNA turnover, regulated by RNase Y, is a critical and tunable mechanism for bacterial stress tolerance and survival.
• Pathogens exploit RNA regulation to navigate the complex pressures of host immunity and antibiotic treatment.