title: Combining mathematical models and statistical methods to understand and predict the dynamics of antibiotic-sensitive mutants in a population of resistant bacteria during experimental evolution.
abstract: Temporarily discontinuing the use of antibiotics has been proposed as a means to eliminate resistant bacteria by allowing sensitive clones to sweep through the population. In this study, we monitored a tetracycline-sensitive subpopulation that emerged during experimental evolution of E. coli K12 MG1655 carrying the multiresistance plasmid pB10 in the absence of antibiotics. The fraction of tetracycline-sensitive mutants increased slowly over 500 generations from 0.1 to 7%, and loss of resistance could be attributed to a recombination event that caused deletion of the tet operon. To help understand the population dynamics of these mutants, three mathematical models were developed that took into consideration recurrent mutations, increased host fitness (selection), or a combination of both mechanisms (full model). The data were best explained by the full model, which estimated a high mutation frequency (lambda = 3.11 x 10(-5)) and a significant but small selection coefficient (sigma = 0.007). This study emphasized the combined use of experimental data, mathematical models, and statistical methods to better understand and predict the dynamics of evolving bacterial populations, more specifically the possible consequences of discontinuing the use of antibiotics.
authors.affiliation: Department of Biological Sciences, Initiative in Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho 83844-3051, USA.
authors.forename: Leen
authors.initials: L
authors.lastname: De Gelder
authors.forename: José M
authors.initials: JM
authors.lastname: Ponciano
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abdo
authors.forename: Paul
authors.initials: P
authors.lastname: Joyce
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Forney
authors.forename: Eva M
authors.initials: EM
authors.lastname: Top
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D048168:Escherichia coli K12 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016013:Likelihood Functions; D008957:Models, Genetic; D009154:Mutation; D012641:Selection, Genetic; D013752:Tetracycline / Q000494:pharmacology; D013753:Tetracycline Resistance / Q000235:genetics* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D013752:Tetracycline