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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

(2004) GENETICS. 168(3). p.1131-1144
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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.
Keywords
FITNESS, DELETION FORMATION, COMPENSATORY MUTATIONS, RECOMBINATION, COST, ADAPTATION, DIRECT REPEATS, TETRACYCLINE-RESISTANCE, DRUG-RESISTANCE, ESCHERICHIA-COLI PLASMIDS

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Chicago
De Gelder, Leen, José M Ponciano, Zaid Abdo, Paul Joyce, Larry J Forney, and Eva M Top. 2004. “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.” Genetics 168 (3): 1131–1144.
APA
De Gelder, L., Ponciano, J. M., Abdo, Z., Joyce, P., Forney, L. J., & Top, E. M. (2004). 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. GENETICS, 168(3), 1131–1144.
Vancouver
1.
De Gelder L, Ponciano JM, Abdo Z, Joyce P, Forney LJ, Top EM. 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. GENETICS. 2004;168(3):1131–44.
MLA
De Gelder, Leen, José M Ponciano, Zaid Abdo, et al. “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.” GENETICS 168.3 (2004): 1131–1144. Print.
@article{765493,
  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.},
  author       = {De Gelder, Leen and Ponciano, Jos{\'e} M and Abdo, Zaid and Joyce, Paul and Forney, Larry J and Top, Eva M},
  issn         = {0016-6731},
  journal      = {GENETICS},
  keyword      = {FITNESS,DELETION FORMATION,COMPENSATORY MUTATIONS,RECOMBINATION,COST,ADAPTATION,DIRECT REPEATS,TETRACYCLINE-RESISTANCE,DRUG-RESISTANCE,ESCHERICHIA-COLI PLASMIDS},
  language     = {eng},
  number       = {3},
  pages        = {1131--1144},
  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},
  url          = {http://dx.doi.org/10.1534/genetics.104.033431},
  volume       = {168},
  year         = {2004},
}

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