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SUMMARY:QLS Seminar -  Function-specific epistasis shapes evolutionary tra
 jectories towards antibiotic resistance
DTSTART;VALUE=DATE-TIME:20260707T080000Z
DTEND;VALUE=DATE-TIME:20260707T090000Z
DTSTAMP;VALUE=DATE-TIME:20260718T015233Z
UID:indico-event-11395@ictp.it
DESCRIPTION:\n	Antibiotic resistance poses a major threat to public health
 : as pathogens become resistant to known antibiotics\, rendering current t
 reatments 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 evolut
 ionary processes in bacterial populations\, and the factors that influence
  the evolution of resistance.\n\n	Bacterial populations can rapidly evolve
  resistance through spontaneous mutations under antibiotic section. Import
 antly\, pre-existing mutations can influence evolution by constraining or 
 opening evolutionary pathways through epistatic interactions. In some case
 s\, 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 res
 istance\, we evolved 258 Escherichia coli gene-deletion strains – mimick
 ing 258 pre-existing mutations – under three antibiotics: trimethoprim\,
  mecillinam\, and nitrofurantoin. These experiments were performed on a ne
 w high-throughput platform capable of running 864 parallel automated evolu
 tion experiments with tight feedback control of population size and select
 ion 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 mi
 nority of pre-existing mutations lead to evolutionary trajectories that si
 gnificantly deviate from this common path. Rather than being predictable f
 rom global epistasis\, these deviations are modulated by function-specific
  epistasis: perturbations to specific cellular functions lead to novel evo
 lutionary trajectories towards resistance. Importantly\, function-specific
  epistasis often slows down resistance evolution. These findings advance o
 ur understanding of the molecular mechanisms of resistance evolution in ba
 cteria and suggest that function-specific epistasis can be exploited as a 
 strategy to combat resistance.\n\n//indico.ictp.it/event/11395/
LOCATION:ICTP Common Area Old SISSA building Second floor
URL://indico.ictp.it/event/11395/
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