Resonant activation: a strategy against bacterial persistence - Quantitative Biology > Molecular NetworksReport as inadecuate




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Abstract: A bacterial colony may develop a small number of cells genetically identicalto, but phenotypically different from other normally growing bacteria. Theseso-called persister cells keep themselves in a dormant state and thus areinsensitive to antibiotic treatment, resulting in serious problems of drugresistance. In this paper, we proposed a novel strategy to -kill- persistercells by triggering them to switch, in a fast and synchronized way, intonormally growing cells that are susceptible to antibiotics. The strategy isbased on resonant activation RA, a well-studied phenomenon in physics wherethe internal noise of a system can constructively facilitate fast andsynchronized barrier crossings. Through stochastic Gilliespie simulation with ageneric toggle switch model, we demonstrated that RA exists in the phenotypicswitching of a single bacterium. Further, by coupling single cell level andpopulation level simulations, we showed that with RA, one can greatly reducethe time and total amount of antibiotics needed to sterilize a bacterialpopulation. We suggest that resonant activation is a general phenomenon inphenotypic transition, and can find other applications such as cancer therapy.



Author: Yan Fu, Meng Zhu, Jianhua Xing

Source: https://arxiv.org/







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