Speaker
Description
No two cells are identical, even when sharing the same genetic code. This variability among phenotypes can be found in cell populations regardless of the complexity of the organism — from mammalian neural tissues to bacterial colonies. In the latter, genetically and morphologically identical bacteria often exhibit a myriad of growth states, resulting in drastic fitness variability. Most of this variance is attributed to stochastic processes. However, we showed that deterministic processes are an essential source of phenotypic heterogeneity. One such process is the asymmetric partitioning of intracellular components that happens upon cell division. When rod-shaped bacteria divide, one daughter inherits a conserved cell pole carrying more damaged components, whereas its sibling inherits a newly synthesized pole. Through single-cell microscopy and microfluidic techniques, we showed that this asymmetry drives a variance in fitness — as expressed by individual growth rates — that trickles down along cell lineages. For instance, by following lineages that inherited either new or conserved poles consecutively, we found that they reach distinct states of physiological equilibrium. Although the system was highly stochastic, this deterministic structure of the population was maintained as long as the population experienced low levels of extrinsic damage. However, under lethal levels of oxidation, asymmetry led to differential survival: lineages inheriting conserved poles arrested division, while those receiving new poles remained in equilibrium. Finally, we showed that these results extend to antibiotic responses, with asymmetry driving the fate of bacterial lineages upon drug exposure. Thus, bacterial asymmetry represents a deterministic source of phenotypic heterogeneity, driving survival in the face of environmental pressures and antibiotic treatments.
