QLS Seminar next week - Tuesday, 7 July at 10h00 - Function-specific epistasis shapes evolutionary trajectories towards antibiotic resistance

[Quantitative Life Sciences]

Dear All,

Next Tuesday, 7 July at 10h00,  Gabriela Petrungaro (University of 
Cologne, Germany) will give a seminar titled:

*"Function-specific epistasis shapes evolutionary trajectories towards 
antibiotic resistance"*

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.

Indico: https://indico.ictp.it/event/11395/

The seminar will take place in the *Common Area, 2nd floor, old SISSA 
building (Via Beirut, 2).*

You are all most welcome to attend!

Best regards,

Erica

Erica Sarnataro
Group Secretary
Quantitative Life Sciences
The Abdus Salam International Centre for Theoretical Physics (ICTP)
Trieste,  Italy
Tel. +39-040-22404623 (NEW PHONE NUMBER)
www.ictp.it/research/qls.aspx
e-mail:qls at ictp.it