Bacterial Cell Differentiation


Four bacterial developmental systems are described. In the dimorphic cell cycle of Caulobacter crescentus, differences in the proteins assembled at cell poles cause cell division to generate a stalked cell rich in regulator DivK‐P, and competent for continued proliferation, and a swarmer cell rich in regulator CtrA‐P, and unable to proliferate until it discards its flagellum and grows a stalk. The other three systems all lead to the formation of spores, but by completely different routes. In Bacillus subtilis, an endospore forms inside a mother cell; in the mycelial Streptomyces coelicolor, long hyphae grow into the air and then turn into chains of spores; whereas in Myxococcus xanthus, which hunts in motile swarms to prey on other bacteria, the swarm aggregates into a mound to form a fruiting body, inside which cells change into spores. The regulatory cascades leading to differentiation evolved completely independently in the four systems, but show some common strategies.

Key Concepts

  • Bacterial cells can be both organisationally and developmentally complex.

  • Bacterial development is usually driven forward by positively acting regulatory cascades, often reinforced by positive feedback loops.

  • Cascades activating bacterial differentiation often respond to environmental or physiological information through the action of repressors or other negatively acting mechanisms.

  • Diverse extracellular signals are often employed to allow communication between cells, leading to coordination of bacterial development.

  • Sporulation has evolved completely independently in different groups of bacteria.

  • Some kinds of protein recur frequently in bacterial developmental systems, including sigma factors, phosphoproteins and proteases.

Keywords: sigma factors; polarity; sporulation; extracellular signalling; cell cycle; phosphorelay; septation

Figure 1.

The differential sequestering of regulatory proteins to cell poles during stages of the dimorphic cell cycle of C. crescentus. (a) Maintaining high levels of CtrA∼P in swarmer cells. At the flagellated pole, PodJ‐stimulated PleC phosphatase activity maintains DivK in its inactive dephosphorylated state, freeing DivL to stimulate the CckA – ChpH – CtrA phosphorelay. Phosphorylated CtrA, in the presence of SciP, prevents replication from the replication origin oriC. (b) Degradation of SciP frees CtrA∼P in the incipient stalked cell, permitting replication and activating transition‐stage transcription. (c) The stalked cell contains DivK in a phosphorylated state and is CtrA‐free. At the pole where a stalk has replaced the swarmer flagellum and pili, PodJ and PleC are replaced by SpmX and DivJ, which phosphorylates DivK. DivK∼P sequesters DivL, and CckA becomes a phosphatase, reversing the phosphorelay and leaving CtrA in a dephosphorylated state in which it is susceptible to proteolytic degradation by ClpXP. This degradation is activated when dephosphorylated CpdR and ClpXP are recruited to the stalked pole by PopA, which has been targeted to the pole by an increase in cyclic‐di‐GMP. At this stage, one of the daughter oriC sequences is held by ParAB at the TipN‐marked pole destined to become the new swarmer pole. (d) Reestablishing CtrA∼P in the incipient swarmer cell. After serving to nucleate the formation of pili and the flagellum, and as an anchor point to ensure proper chromosome segregation, TipN relocates to the ingrowing cell‐division septum. At the new flagellar pole, PleC (with PodJ) dephosphorylates DivK, and the phosphorelay to newly synthesised CtrA is reestablished (see (a)).

Figure 2.

The execution of successive decisions leading to sporulation of B. subtilis. (a) Sporulation is one of the multiple developmental options open to undifferentiated stationary phase cells. Developmental direction is determined by the phosphorylation states of three key regulatory proteins (blue shading). The directions are made mutually exclusive by cross‐repression, enabling genetically identical cells in a population to follow different developmental pathways (Lo'pez and Kolter, ). (b) Physiological signals (blue shading) are integrated by a phosphorelay (boldface type) to determine the level of phosphorylation of the key activator SpoOA. The phosphorelay is regulated by the balance of kinases (Kin) and phosphatases (Rap, SpoIIE), which are in turn regulated by cascades of negatively acting steps. (c) Criss‐cross activation of stage‐ and compartment‐specific sigma factors, which guide RNA polymerase to appropriate sporulation genes.

Figure 3.

Decision‐making during the development of a S. coelicolor colony. (a) Blue shading: to avoid premature differentiation, the global regulator BldD represses genes for AdpA, BldN (a sigma factor) and BldM, three key activators of morphological development. The progression of aerial hyphae into chains of spores (pink shading) is initiated by WblA, and carried through by the Whi regulatory protein cascade, including the sigma factor encoded by whiG. The placement of sporulation septa involves the actinomycete‐specific proteins SsgA and SsgB. Yellow‐shaded proteins belong to the actinobacteria‐specific Wbl family of regulatory proteins. (b) AdpA is at the heart of a complex centre of regulatory inputs and outputs. (c) Stages in the activation of an extracellular protease cascade. Grey shading: first stage of cascade, in which two distinct inhibitory activities of Sti (red ovals) inhibit general proteases (upper part) and target‐specific proteases with special P‐domains (lower part). To the right of grey area: specific Sti‐inactivating proteases eliminate Sti, releasing general proteases to recycle nutrients and target‐specific proteases to process proenzymes needed for developmental progression (Chater et al., ).

Figure 4.

Motility‐driven multicellular differentiation of M. xanthus. (a) Motility reversal. Poles are marked by a response regulator, RomR (blue shading), that nucleates polar complexes, which differ depending on the phosphorylation state of RomR. At the leading pole, with its motility apparatus (type 4 pili, PilB, Agl proteins associated with gliding), RomR is phosphorylated, and stimulates the binding of GTP by the GTPase MglA, whereas the GTPase‐activating protein MglB concentrated mainly at the lagging pole by unphosphorylated RomR converts MglA:GTP to MglA:GDP. Polarity is reversed when the rate of RomR phosphorylation drops. This is a function of the ‘frizilator’ (pink shading), in which negative feedback results in oscillation. (b) A cascade of six EBPs (blue shading) establishes developmentally important A‐signalling (pink shading) and C‐signalling (pale orange shading). The combined action of these signals causes reductions in polarity reversal, seen as rippling of the swarm. The resulting end‐to‐end cell–cell contacts cause enhanced C‐signal accumulation, successively activating gene sets for aggregation and sporulation.



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Further Reading

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How to Cite close
Chater, Keith F(Nov 2013) Bacterial Cell Differentiation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001422.pub2]