A bacteria colony may develop a small number of cells genetically identical  , but phenotypically different from the majority cells in the populations . These so-called persister cells  are insensitive to antibiotics treatment, and contribute to the serious problem of drug resistance. Resonant activation (RA) is a well-studied phenomenon in thermally activated barrier crossing events, where internal noise can constructively facilitate the barrier crossing . Through stochastic Gilliespie simulation with a generic toggle switch model, we demonstrated that the phenomenon also exist for cell phenotype switching . Then we used coupled single cell and population simulations to demonstrate that one can greatly reduce the time and the total amount of antibiotics needed to extinct a bacteria populationwith RA. We also suggested that RA can find application in other situations such as cancer radiotherapy .
A bacterial colony may develop a small number of cells genetically identical to , but phenotypically different from other normally growing bacteria . These so-called persister cells keep themselves in a dormant state and thus are insensitive to antibiotic treatment, resulting in serious problems of drug resistance. In this paper, we proposed a novel strategy to "kill" persister cells by triggering them to switch, in a fast and synchronized way, into normally growing cells that are susceptible to antibiotics. The strategy is based on resonant activation (RA) , a well-studied phenomenon in physics where the internal noise of a system can constructively facilitate fast and synchronized barrier crossings . Through stochastic Gilliespie simulation with a generic toggle switch model, we demonstrated that RA exists in the phenotypic switching of a single bacterium. Further, by coupling single cell level and population level simulations, we showed that with RA, one can greatly reduce the time and total amount of antibiotics needed to sterilize a bacterial population. We suggest that resonant activation is a general phenomenon in phenotypic transition, and can find other applications such as cancer therapy .
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bacteria
bacterial
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to
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the majority cells in the populations
other normally growing bacteria
A
keep themselves in a dormant state and thus
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antibiotics treatment, and contribute to the serious problem
antibiotic treatment, resulting in serious problems
R
Resonant
In this paper, we proposed a novel strategy to "kill" persister cells by triggering them to switch, in a fast and synchronized way, into normally growing cells that are susceptible to antibiotics. The strategy is based on resonant
R
is
,
R
thermally activated barrier crossing events, where internal noise
physics where the internal noise of a system
R
the barrier crossing
fast and synchronized barrier crossings
R
the phenomenon also exist for cell phenotype switching . Then we used coupled single cell and population simulations to demonstrate that
RA exists in the phenotypic switching of a single bacterium. Further, by coupling single cell level and population level simulations, we showed that with RA,
D
the
R
extinct a bacteria populationwith RA. We also suggested that RA can find application in other situations
sterilize a bacterial population. We suggest that resonant activation is a general phenomenon in phenotypic transition, and can find other applications
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radiotherapy
therapy