Tan2012 - Antibiotic Treatment, Inoculum Effect

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Short description
Tan2012 - Antibiotic Treatment, Inoculum Effect

The efficacy of many antibiotics decreases with increasing bacterial density, a phenomenon called the ‘inoculum effect’ (IE). This study reveals that, for ribosome-targeting antibiotics, IE is due to bistable inhibition of bacterial growth, which reduces the efficacy of certain treatment frequencies.

This model is described in the article:

Tan C, Phillip Smith R, Srimani JK, Riccione KA, Prasada S, Kuehn M, You L.
Mol Syst Biol. 2012 Oct 9; 8:617

Abstract:

The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.

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Format
SBML (L2V1)
Related Publication
  • The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.
  • Tan C, Smith RP, Srimani JK, Riccione KA, Prasada S, Kuehn M, You L
  • Molecular Systems Biology , 0/ 2012 , Volume 8 , pages: 617
  • Department of Biomedical Engineering, Duke University, Durham, NC, USA.
  • The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.
Contributors
Cheemeng Tan

Metadata information

is
BioModels Database MODEL1208300000
BioModels Database BIOMD0000000425
isDescribedBy
PubMed 23047527
hasTaxon
isVersionOf
hasProperty
Human Disease Ontology bacterial infectious disease
Curation status
Curated
  • Model originally submitted by : Cheemeng Tan
  • Submitted: 30-Aug-2012 16:19:13
  • Last Modified: 10-Oct-2014 11:47:25
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 10-Oct-2014 11:47:25
    • Submitted by: Cheemeng Tan
    • With comment: Current version of Tan2012 - Antibiotic Treatment, Inoculum Effect
  • Version: 1 public model Download this version
    • Submitted on: 30-Aug-2012 16:19:13
    • Submitted by: Cheemeng Tan
    • With comment: Original import of Tan_and_Smith2012_Antibiotic_InoculumEffect
Curator's comment:
(added: 01 Nov 2012, 15:23:20, updated: 01 Nov 2012, 15:23:20)
The model reproduces figure 1b of the reference publication, when delta is set to 1e-04. The plot data were obtained by simulating the model using Copasi v4.8 (Build 35). The plot was generated using Gnuplot.