Bacterial Cell Differentiation

Abstract

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.

close

References

Banse AV, Chastanet A, Rahn‐Lee L, Hobbs EC and Losick R (2008) Parallel pathways of repression and antirepression governing the transition to stationary phase in Bacillus subtilis. Proceedings of the National Academy of Sciences of the USA 105(40): 15547–15552. 10.1073/pnas.0805203105. PMID: 18840696.

Bibb MJ, Domonkos A, Chandra G and Buttner MJ (2012) Expression of the chaplin and rodlin hydrophobic sheath proteins in Streptomyces venezuelae is controlled by σ(BldN) and a cognate anti‐sigma factor, RsbN. Molecular Microbiology 84(6): 1033–1049. 10.1111/j.1365‐2958.2012.08070.x. Epub 14 May 2012. PMID: 22582857.

Chandra G and Chater KF (2013) Developmental biology of Streptomyces from the perspective of 100 actinobacterial genome sequences. FEMS Microbiology Reviews (in press).

Chater KF, Biró S, Lee KJ, Palmer T and Schrempf H (2010) The complex extracellular biology of Streptomyces. FEMS Microbiology Reviews 34(2): 171–198. 10.1111/j.1574‐6976.2009.00206.x. Epub 15 Dec 2009. Review. PMID: 20088961.

Coen E (2012) Cells to Civilizations. Princeton, New Jersey, USA: Princeton University Press.

Curtis PD and Brun YV (2010) Getting in the loop: regulation of development in Caulobacter crescentus. Microbiology and Molecular Biology Reviews 74(1): 13–41. 10.1128/MMBR.00040‐09. Review. PMID: 20197497.

Fujita M and Losick R (2005) Evidence that entry into sporulation in Bacillus subtilis is governed by a gradual increase in the level and activity of the master regulator Spo0A. Genes & Development 19(18): 2236–2244. PMID: 16166384.

Giglio KM, Caberoy N, Suen G, Kaiser D and Garza AG (2011) A cascade of coregulating enhancer binding proteins initiates and propagates a multicellular developmental program. Proceedings of the National Academy of Sciences of the USA 108(32): E431–439. 10.1073/pnas.1105876108. Epub 13 Jun 2011. PMID: 21670274.

Gora KG, Cantin A, Wohlever M et al. (2013) Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus. Molecular Microbiology 87(6): 1277–1289.

den Hengst CD, Tran NT, Bibb MJ et al. (2010) Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Molecular Microbiology 78(2): 361–379. PMID: 20979333.

Higgins D and Dworkin J (2012) Recent progress in Bacillus subtilis sporulation. FEMS Microbiology Reviews 36(1): 131–148. 10.1111/j.1574‐6976.2011.00310.x. Epub 25 Oct 2011. Review. PMID: 22091839.

Jakimowicz D and van Wezel GP (2012) Cell division and DNA segregation in Streptomyces: how to build a septum in the middle of nowhere? Molecular Microbiology 85(3): 393–404. 10.1111/j.1365‐2958.2012.08107.x. Epub 11 Jun 2012. Review. PMID: 22646484.

Kaiser D, Robinson M and Kroos L (2010) Myxobacteria, polarity, and multicellular morphogenesis. Cold Spring Harbor Perspectives in Biology 2(8): 10.1101/cshperspect.a000380. Epub 7 Jul 2010. Review. PMID: 20610548.

Keilberg D, Wuichet K, Drescher F and Søgaard‐Andersen L (2012) A response regulator interfaces between the Frz chemosensory system and the MglA/MglB GTPase/GAP module to regulate polarity in Myxococcus xanthus. PLoS Genetics 8(9): e1002951. 10.1371/journal.pgen.1002951. Epub 13 Sep 2012. PMID: 23028358.

Kirkpatrick CL and Viollier PH (2012) Decoding Caulobacter development. FEMS Microbiology Reviews 36(1): 193–205. 10.1111/j.1574‐6976.2011.00309.x. Epub 24 Oct 2011. Review. PMID: 22091823.

Konovalova A, Petters T and Søgaard‐Andersen L (2010) Extracellular biology of Myxococcus xanthus. FEMS Microbiology Reviews 34(2): 89–106. 10.1111/j.1574‐6976.2009.00194.x. Epub 20 Oct 2009. Review. PMID: 19895646.

Liu G, Chater KF, Chandra G, Niu G and Tan H (2013) Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiology and Molecular Biology Reviews 77(1): 112–143. 10.1128/MMBR.00054‐12. PMID: 23471619.

López D and Kolter R (2010) Extracellular signals that define distinct and coexisting cell fates in Bacillus subtilis. FEMS Microbiology Reviews 34(2): 134–149. 10.1111/j.1574‐6976.2009.00199.x. Epub 23 Nov 2009. Review. PMID: 20030732.

Ohnishi Y and Horinouchi S (2004) The A‐factor regulatory cascade that leads to morphological development and secondary metabolism in Streptomyces. Biofilms 1: 319–328.

Tojo S, Hirooka K and Fujita Y (2013) Expression of kinA and kinB of Bacillus subtilis, necessary for sporulation initiation, is under positive stringent transcription control Journal of Bacteriology 195(8): 1656–1665. 10.1128/JB.02131‐12. Epub 1 Feb 2013. PMID: 23378509.

Willemse J, Mommaas AM and van Wezel GP (2012) Constitutive expression of ftsZ overrides the whi developmental genes to initiate sporulation of Streptomyces coelicolor. Antonie van Leeuwenhoek 101(3): 619–632. 10.1007/s10482‐011‐9678‐7. Epub 24 Nov 2011. PMID: 22113698.

Zhang G, Tian Y, Hu K et al. (2012a) Importance and regulation of inositol biosynthesis during growth and differentiation of Streptomyces. Molecular Microbiology 83(6): 1178–1194. 10.1111/j.1365‐2958.2012.08000.x. Epub 24 Feb 2012. PMID: 22329904.

Zhang Y, Ducret A, Shaevitz J and Mignot T (2012b) From individual cell motility to collective behaviors: insights from a prokaryote, Myxococcus xanthus. FEMS Microbiology Reviews 36(1): 149–164. 10.1111/j.1574‐6976.2011.00307.x. Epub 3 Oct 2011. Review. PMID: 22091711.

Zhang Y, Guzzo M, Ducret A, Li YZ and Mignot T (2012c) A dynamic response regulator protein modulates G‐protein‐dependent polarity in the bacterium Myxococcus xanthus. PLoS Genetics 8(8): e1002872. 10.1371/journal.pgen.1002872. Epub 16 Aug 2012. PMID: 22916026.

Further Reading

Chater KF (2011) Differentiation in Streptomyces: the properties and programming of diverse cell‐types. In: Dyson P (ed.) Streptomyces: Molecular Biology and Biotechnology, p. 43–86. Norfolk, UK: Caister Academic Press.

Errington J (2013) L‐form bacteria, cell walls and the origins of life. Open Biology 3(1): 120143. 10.1098/rsob.120143. PMID: 23303308.

Flärdh K, Richards DM, Hempel AM, Howard M and Buttner MJ (2012) Regulation of apical growth and hyphal branching in Streptomyces. Current Opinion in Microbiology 15(6): 737–743. 10.1016/j.mib.2012.10.012. Epub 12 Nov 2012. Review. PMID: 23153774.

Kaimer C, Berleman JE and Zusman DR (2012) Chemosensory signaling controls motility and subcellular polarity in Myxococcus xanthus. Current Opinion in Microbiology 15(6): 751–757. 10.1016/j.mib.2012.10.005. Epub 8 Nov 2012. Review. PMID: 23142584.

Kumar K, Mella‐Herrera RA and Golden JW (2010) Cyanobacterial heterocysts. Cold Spring Harbor Perspectives in Biology 2(4): 10.1101/cshperspect.a000315. Epub 24 Feb 2010. Review. PMID: 20452939.

McAdams HH and Shapiro L (2011) The architecture and conservation pattern of whole‐cell control circuitry. Journal of Molecular Biology 409(1): 28–35. 10.1016/j.jmb.2011.02.041. Epub 1 Mar 2011. PMID: 21371478.

Nan B and Zusman DR (2011) Uncovering the mystery of gliding motility in the myxobacteria. Annual Review of Genetics 45: 21–39. 10.1146/annurev‐genet‐110410‐132547. Epub 9 Sep 2011. Review. PMID: 21910630.

Shapiro L, McAdams HH and Losick R (2009) Why and how bacteria localize proteins. Science 326(5957): 1225–1228. 10.1126/science.1175685. Review. PMID: 19965466.

Vlamakis H, Chai Y, Beauregard P, Losick R and Kolter R (2013) Sticking together: building a biofilm the Bacillus subtilis way. Nature Reviews Microbiology 11(3): 157–168. 10.1038/nrmicro2960. Epub 28 Jan 2013. Review. PMID: 23353768.

Wu LJ and Errington J (2011) Nucleoid occlusion and bacterial cell division. Nature Reviews Microbiology 10(1): 8–12. 10.1038/nrmicro2671. PMID: 22020262.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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