Transforming antibiotic tolerance research through genomics

Abstract

Antibiotic tolerance is an increasingly recognised contributor to treatment failure. Integrating genomics with laboratory evolution and functional screening has shifted emphasis from studying tolerance as a transient, non-heritable phenotype to recognising its genetic underpinnings. These approaches reveal pathways that shape antibiotic survival beyond dormant-cell models. However, most insights derive from laboratory systems, leaving their clinical relevance unresolved. In this review, we discuss advances in genome-wide analyses of tolerance and their potential to identify candidate genes and variants in patient-derived isolates, resolve genetic architecture and epistasis, and uncover influences on resistance evolution, ultimately advancing the development of diagnostic and therapeutic strategies.