Abstract
Transfer RNAs (tRNAs) and their modifications are central to bacterial translation and physiology, yet their roles in stress adaptation remain underexplored. While extensively studied in eukaryotes, and linked to diseases, bacterial tRNA modifications are only recently gaining attention. This review highlights emerging insights into how tRNA modifications and associated enzymes contribute to bacterial survival under oxidative and antibiotic stresses, both disrupting proteostasis. We examine the environmental and physiological stresses bacteria encounter, focussing on reactive oxygen species and sub-lethal antibiotic exposure. These stresses challenge proteome integrity and trigger adaptive responses involving key stress regulators. We explore the expanding field of bacterial epitranscriptomics, detailing the diversity, dynamics and structural impact of tRNA modifications, and how they influence selective translation. Central to this is the concept of modification tunable transcripts, linking specific codon usage patterns to stress-responsive translation reprogramming. Beyond their catalytic roles, tRNA-modifying enzymes also have additional functions. We discuss this dual functionality and its broader implications for bacterial adaptability. By integrating recent technological advances and conceptual models, this review underscores the potential of targeting tRNA modifications as a novel strategy to combat bacterial pathogenicity and antibiotic resistance. With many aspects still unresolved, the study of bacterial tRNA modifications promises rich opportunities for discovery and therapeutic innovation.