Rafael Peña-Miller: Evolution of antibiotic resistance in fluctuating environments: the adaptive value of plasmid-mediated heterozygosis

  • Date: Aug 10, 2017
  • Time: 02:00 PM - 03:00 PM (Local Time Germany)
  • Speaker: Rafael Peña-Miller from the UNAM Morelos, México
  • For more information, please check http://penamiller.com/
  • Location: MPI Plön
  • Room: Lecture hall
  • Host: Michael Sieber


Bacterial communities implement different strategies to survive in
unpredictable and hostile environments. Sensing the surroundings and
regulating the metabolic machinery accordingly is a pervasive mechanism
in microbial survival, but responsive regulation may not be optimal if
the environmental signal is unreliable or if the time scale of metabolic
regulation is larger than the frequency of environmental fluctuation.
Alternatively, bacterial populations can be composed of multiple
sub-populations, each expressing a different phenotype. A series of
studies have identified a wide range of molecular mechanisms that allow
the stable co-existence of multiple phenotypes in the population: from
random binding kinetics of promoters and stochastic partitioning during
cell division, to the amplification of noisy responses to biochemical
signals in metabolic pathways. Here we propose an alternative source of
intrinsic phenotypic noise: plasmid copy number variation. Using an
interdisciplinary approach that combines computational and mathematical
modelling with single-cell microfluidics and population-level
experimental evolution, we will show that multicopy plasmids can produce
a heterogeneous population that allows bacterial communities to
implement bet-hedging strategies. Furthermore, using a well
characterised experimental system of drug resistance evolution (plasmid
mediated TEM-1 evolution towards Ceftazidime resistance in E. coli) we
will show that mutations in genes carried in multicopy plasmids yield
periods of heterozygosis that can be beneficial in dynamic environments
with fluctuating selection regimes.

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