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Genetics, Vol. 168, 1131-1144, November 2004, Copyright © 2004
doi:10.1534/genetics.104.033431
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
Leen De Gelder*,
José M. Ponciano
,
Zaid Abdo,
Paul Joyce,
Larry J. Forney* and
Eva M. Top*,1
* Department of Biological Sciences, Initiative in Bioinformatics and Evolutionary Studies (IBEST), University of Idaho, Moscow, Idaho 83844-3051
Department of Mathematics, Division of Statistics, Initiative in Bioinformatics and Evolutionary Studies (IBEST), University of Idaho, Moscow, Idaho 83844-1103
1 Corresponding author: Department of Biological Sciences, 252 Life Sciences S., University of Idaho, Moscow, ID 83844-3051.
E-mail: evatop{at}uidaho.edu
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 (
= 3.11 x 10–5) and a significant but small selection coefficient (
= 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.
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