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"Biological Physics Seminar: Evolution of lag time as an optimization process" | The Racah Institute of Physics

"Biological Physics Seminar: Evolution of lag time as an optimization process"

Date: 
Tue, 31/03/201514:00-15:30
Location: 
Danciger B building, Seminar room
Lecturer: Mr. Ofer Fridman
Affiliation: Racah Institute of Physics,
Hebrew University of Jerusalem
Abstract:
The great therapeutic achievements of antibiotics
have been dramatically undermined by the
evolution of bacterial strategies that overcome
antibiotic stress. These strategies fall into two
classes. ‘Resistance’ makes it possible for a
microorganism to grow in the constant presence
of the antibiotic, provided that the concentration
of the antibiotic is not too high. ‘Tolerance’
allows a microorganism to survive antibiotic
treatment, even at high antibiotic concentrations,
as long as the duration of the treatment is limited.
Although both resistance and tolerance are
important reasons for the failure of antibiotic
treatments, the evolution of resistance is much
better understood than that of tolerance. In my
research I followed the evolution of bacterial
populations under intermittent exposure to the
high concentrations of antibiotics used in the
clinic and characterized the evolved strains in
terms of both resistance and tolerance. I found
that all strains adapted by specific genetic
mutations, which became fixed in the evolved
populations. By monitoring the phenotypic
changes at the population and single-cell levels, I
found that the first adaptive change to antibiotic
stress was the development of tolerance through
a major adjustment in the single-cell lag-time
distribution, without a change in resistance.
Strikingly, I found that the lag time of bacteria
before regrowth was optimized to match the
duration of the antibiotic-exposure interval.
Whole genome sequencing of the evolved strains
and restoration of the wild-type alleles allowed
us to identify target genes involved in this
antibiotic-driven phenotype: ‘tolerance by lag’
(tbl).
The evolution of the lag-time distribution is a
remarkable demonstration of an adaptation not to
the specific nature of an environmental stress but
to its duration. Not only does this finding
illustrate that temporal parameters associated
with growth can be readily changed during
evolution, but also the correspondence between
stress duration and the timescale of the evolved
phenotypes shows how fine-tuned this adaptation
can be.