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BIOMD0000000425 - Tan2012 - Antibiotic Treatment, Inoculum Effect


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Reference Publication
Publication ID: 23047527
Tan C, Smith RP, Srimani JK, Riccione KA, Prasada S, Kuehn M, You L.
The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.
Mol. Syst. Biol. 2012; 8: 617
Department of Biomedical Engineering, Duke University, Durham, NC, USA.  [more]
Original Model: BIOMD0000000425.origin
Submitter: Cheemeng Tan
Submission ID: MODEL1208300000
Submission Date: 30 Aug 2012 16:19:13 UTC
Last Modification Date: 10 Oct 2014 11:47:25 UTC
Creation Date: 01 Nov 2012 15:23:56 UTC
Encoders:  Vijayalakshmi Chelliah
   Cheemeng Tan
set #1
bqbiol:hasProperty Human Disease Ontology bacterial infectious disease
set #2
bqbiol:occursIn Taxonomy Escherichia coli
bqbiol:isVersionOf Gene Ontology cellular response to antibiotic
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


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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Publication ID: 23047527 Submission Date: 30 Aug 2012 16:19:13 UTC Last Modification Date: 10 Oct 2014 11:47:25 UTC Creation Date: 01 Nov 2012 15:23:56 UTC
Mathematical expressions
reaction_1 reaction_3 reaction_2 reaction_4
Physical entities
Compartments Species
cell ribosome concentration    
Reactions (4)
 reaction_1  → [ribosome concentration];  
 reaction_3 [ribosome concentration] → ;   {ribosome concentration}
 reaction_2  → [ribosome concentration];   {ribosome concentration}
 reaction_4 [ribosome concentration] → ;   {ribosome concentration}
 cell Spatial dimensions: 3.0  Compartment size: 1.0
 ribosome concentration
Compartment: cell
Initial amount: 1.0
reaction_1 (1)
Value: 0.001
reaction_3 (1)
Value: 1.0
reaction_2 (1)
Value: 0.5
reaction_4 (3)
Value: 5.0E-6
Value: 1.0E-5
Value: 1.0E-5
Representative curation result(s)
Representative curation result(s) of BIOMD0000000425

Curator's comment: (updated: 01 Nov 2012 15:23:20 GMT)

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.