Phenotypic Heterogeneity ________________________________________________

Joyoti Basu, Indrani Bose, Manikuntala Kundu

Phenotypic Heterogeneity: strategy adopted by microorganisms to cope with stress

Stochastic switching can lead to phenotypic heterogeneity within isogenic cellular populations, and this could underpin the heterogeneous responses of some bacterial pathogens to particular host niches.  This issue is being addressed using mycobacteria as the model and efforts are being made to understand the key events associated with a switch to the persistent phenotype. Our key findings are:


  Time course of rel-GFP expression



Evidence of hysteresis from flow-cytometry data

  • Positive feedback and gene expression noise are responsible for generation of phenotypic heterogeneity in the form of two distinct subpopulations.
  • Experimental evidence of hysteresis, a hallmark of bistable GE is further obtained.
  • Distribution of GFP levels at any time is a linear combination of Gaussian and Lognormal distributions corresponding to two subpopulations, normal and persister.
  • Possible origin of bistability is based on positive feedback which may originate from both regulated GE as well as growth retardation due to protein synthesis. (see reviews, Pomerening, Curr. Opin. in Biotechnology 19, 381 (2008), Fraser et al., Molecular Microbiology 71, 1333 (2009), Singh et al., Curr. Opin. in Microbiol. 12, 460 (2009), Sachdeva et al., FEBS Journal 277, 605 (2010))
Further details: Positive feedback and noise activate the stringent response regulator Rel in mycobacteria by Sureka K., Ghosh B., Dasgupta A., Basu J. , Kundu M.  and Bose I. , PLoS One 3, e1771 (2008)