Starts 7 Jul 2026 10:00
Ends 7 Jul 2026 11:00
Central European Time
QLS Seminar - Function-specific epistasis shapes evolutionary trajectories towards antibiotic resistance
ICTP
Common Area Old SISSA building Second floor
Via Beirut, 2
Antibiotic resistance poses a major threat to public health: as pathogens become resistant to known antibiotics, rendering current treatments ineffective, the number of new antibiotics approved for use is decreasing. The consequent need of novel treatment strategies claims for a better understanding of how antibiotic resistance emerges from the evolutionary processes in bacterial populations, and the factors that influence the evolution of resistance.
Bacterial populations can rapidly evolve resistance through spontaneous mutations under antibiotic section. Importantly, pre-existing mutations can influence evolution by constraining or opening evolutionary pathways through epistatic interactions. In some cases, global epistasis patterns allow evolutionary pathways to be predicted. In other cases, idiosyncratic epistasis makes evolution less predictable. To systematically study this phenomenon in the context of antibiotic resistance, we evolved 258 Escherichia coli gene-deletion strains – mimicking 258 pre-existing mutations – under three antibiotics: trimethoprim, mecillinam, and nitrofurantoin. These experiments were performed on a new high-throughput platform capable of running 864 parallel automated evolution experiments with tight feedback control of population size and selection pressure, allowing a quantitative analysis of resistance trajectories. We show that the evolution of antibiotic resistance is highly repeatable, following a common path across most genetic backgrounds. However, a minority of pre-existing mutations lead to evolutionary trajectories that significantly deviate from this common path. Rather than being predictable from global epistasis, these deviations are modulated by function-specific epistasis: perturbations to specific cellular functions lead to novel evolutionary trajectories towards resistance. Importantly, function-specific epistasis often slows down resistance evolution. These findings advance our understanding of the molecular mechanisms of resistance evolution in bacteria and suggest that function-specific epistasis can be exploited as a strategy to combat resistance.