title: Regulatory design governing progression of population growth phases in bacteria.
abstract: It has long been noted that batch cultures inoculated with resting bacteria exhibit a progression of growth phases traditionally labeled lag, exponential, pre-stationary and stationary. However, a detailed molecular description of the mechanisms controlling the transitions between these phases is lacking. A core circuit, formed by a subset of regulatory interactions involving five global transcription factors (FIS, HNS, IHF, RpoS and GadX), has been identified by correlating information from the well- established transcriptional regulatory network of Escherichia coli and genome-wide expression data from cultures in these different growth phases. We propose a functional role for this circuit in controlling progression through these phases. Two alternative hypotheses for controlling the transition between the growth phases are first, a continuous graded adjustment to changing environmental conditions, and second, a discontinuous hysteretic switch at critical thresholds between growth phases. We formulate a simple mathematical model of the core circuit, consisting of differential equations based on the power-law formalism, and show by mathematical and computer-assisted analysis that there are critical conditions among the parameters of the model that can lead to hysteretic switch behavior, which--if validated experimentally--would suggest that the transitions between different growth phases might be analogous to cellular differentiation. Based on these provocative results, we propose experiments to test the alternative hypotheses.
authors.affiliation: Departamento de Ingeniería Genética, Cinvestav, Irapuato, Guanajuato, México. amartinez@ira.cinvestav.mx
authors.forename: Agustino
authors.initials: A
authors.lastname: Martínez-Antonio
authors.forename: Jason G
authors.initials: JG
authors.lastname: Lomnitz
authors.forename: Santiago
authors.initials: S
authors.lastname: Sandoval
authors.forename: Maximino
authors.initials: M
authors.lastname: Aldana
authors.forename: Michael A
authors.initials: MA
authors.lastname: Savageau
mesh_terms: D051777:AraC Transcription Factor / Q000235:genetics / Q000378:metabolism; D002876:Chromosomes, Bacterial / Q000235:genetics; D015169:Colony Count, Microbial; D003198:Computer Simulation; D004261:DNA Replication / Q000235:genetics; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D008957:Models, Genetic; D010641:Phenotype; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051777:AraC Transcription Factor; D029968:Escherichia coli Proteins; C446316:GadX protein, E coli; D014157:Transcription Factors