Open AccessWhen to wake up? The optimal waking-up strategies for starvation-induced persistence
Author(s) -
Yusuke Himeoka,
Namiko Mitarai
Publication year - 2021
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1008655
Subject(s) - lag , multidrug tolerance , antibiotics , persistence (discontinuity) , population , lag time , biology , bacteria , biological system , computer science , microbiology and biotechnology , genetics , medicine , engineering , computer network , geotechnical engineering , environmental health , biofilm
Prolonged lag time can be induced by starvation contributing to the antibiotic tolerance of bacteria. We analyze the optimal lag time to survive and grow the iterative and stochastic application of antibiotics. A simple model shows that the optimal lag time can exhibit a discontinuous transition when the severeness of the antibiotic application, such as the probability to be exposed the antibiotic, the death rate under the exposure, and the duration of the exposure, is increased. This suggests the possibility of reducing tolerant bacteria by controlled usage of antibiotics application. When the bacterial populations are able to have two phenotypes with different lag times, the fraction of the second phenotype that has different lag time shows a continuous transition. We then present a generic framework to investigate the optimal lag time distribution for total population fitness for a given distribution of the antibiotic application duration. The obtained optimal distributions have multiple peaks for a wide range of the antibiotic application duration distributions, including the case where the latter is monotonically decreasing. The analysis supports the advantage in evolving multiple, possibly discrete phenotypes in lag time for bacterial long-term fitness.