Evolutionary Trade-offs Between Antimicrobial Resistance and Virulence in Pseudomonas aeruginosa
Antimicrobial resistance (AMR) threatens antibiotic efficacy, yet its evolutionary consequences for pathogen virulence and growth remain poorly resolved. This thesis addresses this gap using Pseudomonas aeruginosa, a multidrug-resistant pathogen capable of both acute toxin-mediated and chronic colonization-based infections. From independently evolved isogenic populations resistant to ciprofloxacin (CIP), piperacillin/tazobactam (PIT), or streptomycin (STR), highly resistant clones were isolated and characterized for resistance levels, growth performance, virulence-associated traits, and infection outcomes in acute and chronic C. elegans models. Whole-genome sequencing was used to identify genetic routes to resistance. Resistance evolution produced antibiotic-specific effects. CIP-resistant clones consistently exhibited reduced growth and virulence, indicating substantial fitness costs. PIT-resistant clones showed pronounced phenotypic heterogeneity, ranging from near–wild-type to strongly impaired phenotypes, reflecting diverse evolutionary trajectories. In contrast, STR-resistant clones largely maintained high growth and virulence despite strong resistance, suggesting minimal pleiotropic cost. Genetic analyses revealed distinct resistance mechanisms across antibiotics, explaining phenotypic divergence beyond MIC values alone. Overall, this work demonstrates that there is no universal resistance–virulence trade-off. Instead, virulence outcomes depend on the biological pathways underlying resistance and their associated fitness costs. By showing that virulence aligns more closely with resistance mechanisms than with resistance magnitude, this thesis highlights a key limitation of current antibiotic stewardship strategies that focus solely on MIC-based resistance metrics.
AMR, Antibiotic Resistance, Virulence, Fitness, Bacteria
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