From stress to survival:Antibiotic adaptation in E. coli
Abstract
This dissertation investigates the intricate mechanisms driving bacterial adaptation to antibiotic pressure, focusing on E. coli resistance to beta-lactams and fluoroquinolones. Through genomic, proteomic, and transcriptomic analyses, this work elucidates the complexity of resistance evolution, highlighting drug-specific responses and underexplored pathways. Chapter 2 examines the adaptation to amoxicillin, revealing that central resistance genes such as dinB and katE play a smaller role than previously assumed. Novel mutations in frdD and amplified regions surrounding the ampC operon suggest intricate metabolic interplay during adaptation. Chapter 3 employs whole-genome sequencing to study fluoroquinolone resistance, uncovering drug-specific mutation profiles among ciprofloxacin, enrofloxacin, levofloxacin, and moxifloxacin. These findings challenge the uniformity of fluoroquinolone mechanisms of action. Chapter 4 explores proteomic responses, particularly in recA knockout mutants, lacking the SOS response, exposed to ciprofloxacin and enrofloxacin. This analysis highlights recA-independent pathways in fluoroquinolone resistance, broadening the understanding of bacterial adaptation. Chapter 5 critiques methodological inconsistencies in antibiotic resistance research, advocating for integrated, standardized approaches to enhance study reliability and applicability. In summary, this dissertation underscores the multifaceted nature of bacterial resistance, emphasizing the need…
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