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The observed heterogeneity is in the form of a bimodal distribution of the expression levels of the Green Fluorescent Protein (GFP) as reporter with the <jats:italic>gfp<\/jats:italic> fused to the promoter of the <jats:italic>rel<\/jats:italic> gene. The stringent response pathway is initiated in the subpopulation with high <jats:italic>rel<\/jats:italic> activity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In the present study, we characterise quantitatively the single cell promoter activity of the three key genes, namely, <jats:italic>mprA<\/jats:italic>, <jats:italic>sigE<\/jats:italic> and <jats:italic>rel<\/jats:italic>, in the stringent response pathway with <jats:italic>gfp<\/jats:italic> as the reporter. The origin of bimodality in the GFP distribution lies in two stable expression states, i.e., bistability. We develop a theoretical model to study the dynamics of the stringent response pathway. The model incorporates a recently proposed mechanism of bistability based on positive feedback and cell growth retardation due to protein synthesis. Based on flow cytometry data, we establish that the distribution of GFP levels in the mycobacterial population at any point of time is a linear superposition of two invariant distributions, one Gaussian and the other lognormal, with only the coefficients in the linear combination depending on time. This allows us to use a binning algorithm and determine the time variation of the mean protein level, the fraction of cells in a subpopulation and also the coefficient of variation, a measure of gene expression noise.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The results of the theoretical model along with a comprehensive analysis of the flow cytometry data provide definitive evidence for the coexistence of two subpopulations with overlapping protein distributions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-5-18","type":"journal-article","created":{"date-parts":[[2011,2,25]],"date-time":"2011-02-25T17:11:12Z","timestamp":1298653872000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Phenotypic heterogeneity in mycobacterial stringent response"],"prefix":"10.1186","volume":"5","author":[{"given":"Sayantari","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamakshi","family":"Sureka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaswar","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indrani","family":"Bose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyoti","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manikuntala","family":"Kundu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,1,27]]},"reference":[{"key":"611_CR1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1146\/annurev.micro.62.081307.163002","volume":"62","author":"JW Veening","year":"2008","unstructured":"Veening JW, Smits WK, Kuipers OP: Bistability, epigenetics and bet-hedging in bacteria. 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