Bacterial cell differentiation enables population level survival strategies

Abstract

Clonal reproduction of unicellular organisms ensures the stable inheritance of genetic information. However, this means of reproduction lacks an intrinsic basis for genetic variation, other than spontaneous mutation and horizontal gene transfer. To make up for this lack of genetic variation, many unicellular organisms undergo the process of cell differentiation to achieve phenotypic heterogeneity within isogenic populations. Cell differentiation is either an inducible or obligate program. Induced cell differentiation can occur as a response to a stimulus, such as starvation or host cell invasion, or it can be a stochastic process. In contrast, obligate cell differentiation is hardwired into the organism's life cycle. Whether induced or obligate, bacterial cell differentiation requires the activation of a signal transduction pathway that initiates a global change in gene expression and ultimately results in a morphological change. While cell differentiation is considered a hallmark in the development of multicellular organisms, many unicellular bacteria utilize this process to implement survival strategies. In this review, we describe well-characterized cell differentiation programs to highlight three main survival strategies used by bacteria capable of differentiation: (i) environmental adaptation, (ii) division of labor, and (iii) bet-hedging.

Keywords: Bacillus subtilis; Caulobacter crescentus; Myxococcus xanthus; bet-hedging; cell differentiation; division of labor; signal transduction.

Fig 1

Examples of induced and obligate bacterial cell differentiation. Many bacteria undergo either induced or obligate cell differentiation. Induced cell differentiation is initiated either in response to a stimulus or stochastically. Obligate cell differentiation is hardwired into the organism’s life cycle. Under starvation conditions, B. subtilis cells differentiate into biofilm-forming cells and metabolically inactive spores. Sporulation requires a coordinated process of asymmetric cell division and spore formation. M. xanthus bacteria also form spores upon nutrient depletion. Swarming M. xanthus cells differentiate into aggregating cells that form a fruiting body consisting of spores. M. xanthus sporulation does not require cell division, but instead entails the complete remodeling of the cytoskeleton and cell wall. Uropathogenic E. coli differentiate into coccoid and filamentous morphologies upon host cell invasion. When infected cells rupture, released bacteria are able to invade neighboring cells, resulting in infection persistence. Caulobacter crescentus is an aquatic bacterium that undergoes obligate differentiation from a replication-incompetent motile swarmer cell to a replicating stationary stalked cell, with each cell cycle. Asymmetric division and cell differentiation are both obligate events, hardwired into Caulobacter’s cell cycle.

Fig 2

The basic framework of signal transduction pathways is broadly conserved. Signal transduction is required in cells across all kingdoms in order to integrate external environmental and internal physiological signals into biological outcomes such as cell differentiation, cell cycle progression, and cellular adaptation. B. subtilis and Caulobacter use two-component systems to integrate signals into the decision of whether or not to differentiate. These signaling pathways are built into complex molecular networks that are not depicted in their entirety here. Receptor tyrosine kinase (RTK)/Ras/mitogen-activated protein kinase (MAPK) signaling pathways are an example of eukaryotic signaling pathways that integrate signals into cell fate and cell proliferation decisions. While the specific proteins and their interactions are not conserved between bacterial and eukaryotic signal transduction pathways, the basic framework of these pathways shares many similarities.