177229
notes: kappa represents the concentration of c rliciting half-maximal activation of its positive feedback
value: 0.5
name: kappa
type: LocalParameter

metaid_0000005
kinetic law: 177142
product: 177130
fast: false
reversible: false
name: reaction_1
type: Reaction

metaid_0000003
is version of: GO:0005623
constant: true
size: 1.0
spatial dimensions: 3.0
name: cell
type: Compartment

BIOMD0000000425
reaction: metaid_0000008
is described by: http://identifiers.org/pubmed/23047527
reaction: metaid_0000006
reaction: metaid_0000005
occurs in: http://identifiers.org/taxonomy/562
creator:
  ORG:
    orgname: Carnegie Mellon University
  n:
    given: Cheemeng
    family: Tan
volume units: volume
created:
  W3 CDTF: Thu Nov 01 15:23:56 GMT 2012
type: SBMLModel
species: metaid_0000004
is: MODEL1208300000
length unit: length
notes: 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: The inoculum effect and band-pass bacterial response to periodic antibiotic treatment. 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. This model is hosted on BioModels Database and identified by: MODEL1208300000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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 Dom…
compartment: metaid_0000003
name: Tan2012 - Antibiotic Treatment, Inoculum Effect
substance units: substance
modified:
  W3 CDTF: Mon Jun 10 12:46:09 BST 2013
is version of: GO:0071236
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
time units: time
curated: true
area units: area
reaction: metaid_0000007

177130
stoichiometry: 1.0
species: metaid_0000004
type: SpeciesReference

metaid_0000007
kinetic law: 177217
modifier: 432648
product: 177204
fast: false
reversible: false
name: reaction_2
type: Reaction

177291
notes: gamma represents the bacterial density
value: 1.0E-5
name: gamma
type: LocalParameter

177204
stoichiometry: 1.0
species: metaid_0000004
type: SpeciesReference

metaid_0000008
kinetic law: 177253
modifier: 432660
reactant: 177241
fast: false
reversible: false
name: reaction_4
type: Reaction

177241
stoichiometry: 1.0
species: metaid_0000004
type: SpeciesReference

metaid_0000006
kinetic law: 177180
modifier: 432636
reactant: 177167
fast: false
reversible: false
name: reaction_3
type: Reaction

metaid_0000004
notes: c represents concentration of ribosomes C
has only substance units: false
in compartment: metaid_0000003
has part: P0A7L0
constant: false
has part: P0AG67
name: ribosome concentration
type: Species
boundary condition: false
initial amount: 1.0
initial concentration: NaN

177167
stoichiometry: 1.0
species: metaid_0000004
type: SpeciesReference

177192
value: 1.0
name: kd
type: LocalParameter

177266
notes: phi represents the applied anitbiotic concentration
value: 5.0E-6
name: phi
type: LocalParameter

177155
notes: alpha represents the basal synthesis rate of c
value: 0.001
name: alpha
type: LocalParameter

177279
notes: the parameter delta lumps the effects of multiple reactions: it increases with decreasing rates of intrinsic or antibiotic-induced degradation of C (ribosomes), increasing dissociation between the antibiotic and C, and increasing export rate of the antibiotic.
value: 1.0E-5
name: delta
type: LocalParameter