Joyoti Basu, Indrani
Phenotypic Heterogeneity: strategy adopted
by microorganisms to cope with stress
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
Evidence of hysteresis
from flow-cytometry data
Rel in mycobacteria by Sureka K., Ghosh B., Dasgupta A., Basu J. , Kundu M. and Bose I. , PLoS
- Positive feedback and gene
expression noise are responsible for generation of phenotypic
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
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.
(2009), Sachdeva et al., FEBS Journal 277, 605 (2010))