The diverse phenotypic and mutational landscape induced by fluoroquinolone treatment

Abstract

Antibiotic resistance poses a critical global health threat, with antibiotic-tolerant cells further complicating treatment by promoting infection relapse and enabling resistance mutations. Though tolerant cells can evolve into resistant strains, their phenotypic and genotypic characteristics are still poorly understood. In this study, we used adaptive laboratory evolution to generate several distinct ofloxacin-resistant mutants and examined their fitness (e.g., lag phase), metabolic traits (e.g., ATP levels), and genetic adaptations through whole-genome sequencing. We uncovered novel findings, including highly tolerant mutants exhibiting unexpectedly low minimum inhibitory concentrations and others with shorter lag phases, challenging conventional patterns in bacterial resistance evolution. Our findings provide critical insights into the diverse pathways and mechanisms underpinning bacterial adaptation, underscoring the complexity of resistance evolution.