Whereas most prokaryotes rely on binary fission for propagation, many species use alternative mechanisms, which include multiple offspring formation and budding, to reproduce. In some bacterial species, these eccentric reproductive strategies are essential for propagation, whereas in others the programmes are used conditionally. Although there are tantalizing images and morphological descriptions of these atypical developmental processes, none of these reproductive structures are characterized at the molecular genetic level. Now, with newly available analytical techniques, model systems to study these alternative reproductive programmes are being developed.
Although binary fission is conceptually simple, complex genetic mechanisms enhance the fidelity of cell division. Based on comparisons of model organisms, there is remarkable flexibility in the evolution of genes that govern this essential process in the Bacteria.
Alternative reproductive modes are found in diverse lineages in the Bacteria. These include modified programmes based on endospore formation, multiple fission of an enlarged or filamentous cell and budding. This review discusses selected lineages that could serve as new models for studying the mechanisms that mediate these unusual reproductive strategies. A phylogenetic perspective is emphasized because model systems can serve as a foundation on which to build hypotheses to study these alternative systems of reproduction and development.
Some low-GC Gram-positive bacteria, such as Metabacterium polyspora, the segmented filamentous bacteria and Epulopiscium spp. have apparently converted a programme of endospore formation into a mode of propagation in which multiple intracellular offspring are produced.
The pleurocapsalean cyanobacteria, such as Stanieria, Myxosarcina, Pleurocapsa and Dermocarpella, use multiple fission of an enlarged cell to produce baeocyte offspring.
To enhance dispersal of offspring, members of the Actinobacteria produce spores on aerial structures. In the case of streptomycetes, terminal cells of the aerial mycelium divide synchronously to produce the uninucleoid cells which become spores. Other Actinobacteria, such as Actinoplanes and Pilimelia, produce complex sporangia in the absence of aerial mycelium formation.
The life cycle of the predatory δ-proteobacterium Bdellovibrio has distinct stages of growth, multiple fission and differentiation to motile attack-phase cells.
A morphologically diverse group of prosthecate α-proteobacteria, including Hyphomonas, Pedomicrobium and Ancalomicrobium, reproduce by budding mechanisms.
Some Planctomycetes also reproduce by budding; currently nothing is known about cell division or reproduction in this bacterial lineage.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Detection and characterization of rice orange leaf phytoplasma infection in rice and Recilia dorsalis
Phytopathology Research Open Access 21 September 2022
Scientific Reports Open Access 09 January 2020
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Lutkenhaus, J. Unexpected twist to the Z ring. Dev. Cell 2, 519–521 (2002).
Donachie, W. D. Co-ordinate regulation of the Escherichia coli cell cycle or the cloud of unknowing. Mol. Microbiol. 40, 779–785 (2001).
Harry, E. J. Bacterial cell division: regulating Z-ring formation. Mol. Microbiol. 40, 795–803 (2001).
Margolin, W. Spatial regulation of cytokinesis in bacteria. Curr. Opin. Microbiol. 4, 647–652 (2001).
Jensen, R. B., Wang, S. C. & Shapiro, L. Dynamic localization of proteins and DNA during a bacterial cell cycle. Nature Rev. Mol. Cell Biol. 3, 167–176 (2002).
Errington, J., Daniel, R. A. & Scheffers, D. J. Cytokinesis in bacteria. Microbiol. Mol. Biol. Rev. 67, 52–65 (2003).
Sherratt, D. J. Bacterial chromosome dynamics. Science 301, 780–785 (2003).
Ryan, K. R. & Shapiro, L. Temporal and spatial regulation in prokaryotic cell cycle progression and development. Annu. Rev. Biochem. 72, 367–394 (2003).
Skerker, J. M. & Laub, M. T. Cell-cycle progression and the generation of asymmetry in Caulobacter crescentus. Nature Rev. Microbiol. 2, 325–337 (2004).
Stephens, C. Prokaryotic development: a new player on the cell cycle circuit. Curr. Biol. 14, R505–R507 (2004).
Wu, L. J. Structure and segregation of the bacterial nucleoid. Curr. Opin. Genet. Dev. 14, 126–132 (2004).
Viollier, P. H. et al. Rapid and sequential movement of individual chromosomal loci to specific subcellular locations during bacterial DNA replication. Proc. Natl Acad. Sci. USA 101, 9257–9262 (2004).
Wu, L. J. & Errington, J. Coordination of cell division and chromosome segregation by a nucleoid occlusion protein in Bacillus subtilis. Cell 117, 915–925 (2004).
Gerdes, K., Moller-Jensen, J., Ebersbach, G., Kruse, T. & Nordstrom, K. Bacterial mitotic machineries. Cell 116, 359–366 (2004).
Lowe, J. & Amos, L. A. Crystal structure of the bacterial cell-division protein FtsZ. Nature 391, 203–206 (1998).
Wang, X. & Lutkenhaus, J. The FtsZ protein of Bacillus subtilis is localized at the division site and has GTPase activity that is dependent upon FtsZ concentration. Mol. Microbiol. 9, 435–442 (1993).
Iyer, L. M., Makarova, K. S., Koonin, E. V. & Aravind, L. Comparative genomics of the FtsK–HerA superfamily of pumping ATPases: implications for the origins of chromosome segregation, cell division and viral capsid packaging. Nucleic Acids Res. 32, 5260–5279 (2004).
Romberg, L. & Levin, P. A. Assembly dynamics of the bacterial cell division protein FtsZ: poised at the edge of stability. Annu. Rev. Microbiol. 57, 125–154 (2003).
Margolin, W. Catching some Zs: a new protein for spatial regulation of bacterial cytokinesis. Cell 117, 850–851 (2004).
Crowley, D. J. & Courcelle, J. Answering the call: coping with DNA damage at the most inopportune time. J. Biomed. Biotechnol. 2, 66–74 (2002).
Kawai, Y., Moriya, S. & Ogasawara, N. Identification of a protein, YneA, responsible for cell division suppression during the SOS response in Bacillus subtilis. Mol. Microbiol. 47, 1113–1122 (2003).
Raskin, D. M. & de Boer, P. A. MinDE-dependent pole-to-pole oscillation of division inhibitor MinC in Escherichia coli. J. Bacteriol. 181, 6419–6424 (1999).
Marston, A. L., Thomaides, H. B., Edwards, D. H., Sharpe, M. E. & Errington, J. Polar localization of the MinD protein of Bacillus subtilis and its role in selection of the mid-cell division site. Genes Dev. 12, 3419–3430 (1998).
Nierman, W. C. et al. Complete genome sequence of Caulobacter crescentus. Proc. Natl Acad. Sci. USA 98, 4136–4141 (2001).
Rothfield, L., Justice, S. & Garcia-Lara, J. Bacterial cell division. Annu. Rev. Genet. 33, 423–448 (1999).
Margolin, W. Themes and variations in prokaryotic cell division. FEMS Microbiol. Rev. 24, 531–548 (2000).
Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y. & Hattori, M. The KEGG resource for deciphering the genome. Nucleic Acids Res. 32, D277–D280 (2004).
Andrews, P. D., Harper, I. S. & Swedlow, J. R. To 5D and beyond: quantitative fluorescence microscopy in the postgenomic era. Traffic 3, 29–36 (2002).
Ostrowski, S. G., Van Bell, C. T., Winograd, N. & Ewing, A. G. Mass spectrometric imaging of highly curved membranes during Tetrahymena mating. Science 305, 71–73 (2004).
Gisselson, L. A., Graneli, E. & Pallon, J. Variation in cellular nutrient status within a population of Dinophysis norvegica (Dinophyceae) growing in situ: single-cell elemental analysis by use of nuclear microprobe. Limnol. Oceanogr. 46, 1237–1242 (2001).
Grossman, A. D. Integration of developmental signals and the initiation of sporulation in B. subtilis. Cell 65, 5–8 (1991).
Eichenberger, P. et al. The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis. PLoS Biol. 2, E328 (2004).
Stragier, P. in Bacillus subtilis and Its Closest Relatives (eds Sonenshein, A. L., Hoch, J. A. & Losick, R.) 519–526 (ASM Press, Washington DC, 2002).
Errington, J. Regulation of endospore formation in Bacillus subtilis. Nature Rev. Microbiol. 1, 117–126 (2003).
Hilbert, D. W. & Piggot, P. J. Compartmentalization of gene expression during Bacillus subtilis spore formation. Microbiol. Mol. Biol. Rev. 68, 234–262 (2004). This current review outlines recent advances in our understanding of endospore formation and provides an exceptional historical insight into the field.
Stragier, P. & Losick, R. Molecular genetics of sporulation in Bacillus subtilis. Annu. Rev. Genet. 30, 297–241 (1996).
Bath, J., Wu, L. J., Errington, J. & Wang, J. C. Role of Bacillus subtilis SpoIIIE in DNA transport across the mother cell–prespore division septum. Science 290, 995–997 (2000).
Levin, P. A. & Losick, R. Transcription factor Spo0A switches the localization of the cell division protein FtsZ from a medial to a bipolar pattern in Bacillus subtilis. Genes Dev. 10, 478–488 (1996).
Ryter, A. Etude morphologique de la sporulation de Bacillus subtilis. Ann. Inst. Pasteur (Paris) 108, 40–60 (1965).
Ben-Yehuda, S., Rudner, D. Z. & Losick, R. RacA, A bacterial protein that anchors chromosomes to the poles. Science 299, 532–536 (2003).
Nicholson, W. L., Munakata, N., Horneck, G., Melosh, H. J. & Setlow, P. Resistance of Bacillus endospores to extreme terrestrial and extraterrestrial environments. Microbiol. Mol. Biol. Rev. 64, 548–572 (2000).
Chatton, É. & Pérard, C. Schizophytes du caecum du cobaye. II Metabacterium polyspora n. g., n. s. C. R. Hebd. Soc. Biol. (Paris) 74, 1232–1234 (1913).
Robinow, C. F. Kurzer hinweis auf Metabacterium polyspora. Z. Tropenmed. Parasitol. 8, 225–227 (1957).
Kunstyr, I., Schiel, R., Kaup, F. J., Uhr, G. & Kirchhoff, H. Giant gram-negative noncultivable endospore-forming bacteria in rodent intestines. Naturwissenschaften 75, 525–527 (1988).
Angert, E. R. & Losick, R. M. Propagation by sporulation in the guinea pig symbiont Metabacterium polyspora. Proc. Natl Acad. Sci. USA 95, 10218–10223 (1998).
Duda, V. I., Labedinsky, A. V., Mushegjan, M. S. & Mitjushina, L. L. A new anaerobic bacterium, forming up to five endospores per cell - Anaerobacter polyendosporus gen. et spec. nov. Arch. Microbiol. 148, 121–127 (1987).
Siunov, A. V. et al. Phylogenetic status of Anaerobacter polyendosporus, an anaerobic, polysporogenic bacterium. Int. J. Syst. Bacteriol. 49, 1119–1124 (1999).
Klaasen, H. L. et al. Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species. Lab. Anim. 27, 141–150 (1993).
Davis, C. P. & Savage, D. C. Habitat, succession, attachment, and morphology of segmented, filamentous microbes indigenous to the murine gastrointestinal tract. Infect. Immun. 10, 948–956 (1974).
Erlandsen, S. L. & Chase, D. G. Morphological alterations in the microvillous border of villous epithelial cells produced by intestinal microorganisms. Am. J. Clin. Nutr. 27, 1277–1286 (1974).
Klaasen, H. L., Koopman, J. P., Poelma, F. G. & Beynen, A. C. Intestinal, segmented, filamentous bacteria. FEMS Microbiol. Rev. 8, 165–180 (1992).
Chase, D. G. & Erlandsen, S. L. Evidence for a complex life cycle and endospore formation in the attached, filamentous, segmented bacterium from murine ileum. J. Bacteriol. 127, 572–583 (1976).
Ferguson, D. J. & Birch-Andersen, A. Electron microscopy of a filamentous, segmented bacterium attached to the small intestine of mice from a laboratory animal colony in Denmark. Acta Pathol. Microbiol. Scand. 87, 247–252 (1979). This is a compelling account of the murine SFB life cycle.
Umesaki, Y., Okada, Y., Imaoka, A., Setoyama, H. & Matsumoto, S. Interactions between epithelial cells and bacteria, normal and pathogenic. Science 276, 964–965 (1997).
Klaasen, H. L. et al. Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice. Infect. Immun. 61, 303–306 (1993).
Fishelson, L., Montgomery, W. L. & Myrberg, A. A. A unique symbiosis in the gut of a tropical herbivorous surgeonfish (Acanthuridae: Teleostei) from the Red Sea. Science 229, 49–51 (1985).
Clements, K. D., Sutton, D. C. & Choat, J. H. Occurrence and characteristics of unusual protistan symbionts from surgeonfishes Ancanthuridae of the Great Barrier Reef Australia. Marine Biol. 102, 403–412 (1989).
Montgomery, W. L. & Pollak, P. E. Epulopiscium fishelsoni n. g., n. s., a protist of uncertain taxonomic affinities from the gut of an herbivorous reef fish. J. Protozool. 35, 565–569 (1988).
Angert, E. R., Clements, K. D. & Pace, N. R. The largest bacterium. Nature 362, 239–241 (1993).
Angert, E. R., Brooks, A. E. & Pace, N. R. Phylogenetic analysis of Metabacterium polyspora: clues to the evolutionary origin of daughter cell production in Epulopiscium species, the largest bacteria. J. Bacteriol. 178, 1451–1456 (1996).
Angert, E. R. & Clements, K. D. Initiation of intracellular offspring in Epulopiscium. Mol. Microbiol. 51, 827–835 (2004). With reference 45, demonstrates the power of fluorescence microscopy in describing developmental processes in bacteria that cannot be cultured in the laboratory.
Kunst, F. et al. The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature 390, 249–256 (1997).
Onyenwoke, R. U., Brill, J. A., Farahi, K. & Wiegel, J. Sporulation genes in members of the low G+C Gram-type-positive phylogenetic branch (Firmicutes). Arch. Microbiol. 182, 182–192 (2004).
Waterbury, J. B. & Stanier, R. Y. Patterns of growth and development in pleurocapsalean cyanobacteria. Microbiol. Rev. 42, 2–44 (1978). This outstanding, lucid monograph describes the developmental patterns of 32 strains of cyanobacteria based on stunning electron micrographs and time-lapse, light microscopy of growing cells.
Mazouni, K., Domain, F., Cassier-Chauvat, C. & Chauvat, F. Molecular analysis of the key cytokinetic components of cyanobacteria: FtsZ, ZipN and MinCDE. Mol. Microbiol. 52, 1145–1158 (2004).
The Development of Drosophila melanogaster (eds. Bate, M. & Arias, A. M.) (Cold Spring Harbor Laboratory Press, New York, 1993).
Chater, K. F. & Hopwood, D. A. in Microbial Differentiation (eds Ashworth, J. M. & Smith, J. E.) 143–160 (Cambridge University Press, Cambridge, 1973).
Chater, K. F. Genetics of differentiation in Streptomyces. Annu. Rev. Microbiol. 47, 685–713 (1993).
Chater, K. F. & Horinouchi, S. Signalling early developmental events in two highly diverged Streptomyces species. Mol. Microbiol. 48, 9–15 (2003).
Flardh, K. Growth polarity and cell division in Streptomyces. Curr. Opin. Microbiol. 6, 564–571 (2003). A cell biological view of recent advances in understanding hyphal growth and spore development in Streptomyces.
Gehring, A. M., Nodwell, J. R., Beverley, S. M. & Losick, R. Genomewide insertional mutagenesis in Streptomyces coelicolor reveals additional genes involved in morphological differentiation. Proc. Natl Acad. Sci. USA 97, 9642–9647 (2000).
Ikeda, H. et al. Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nature Biotechnol. 21, 526–531 (2003).
Bentley, S. D. et al. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417, 141–147 (2002).
McCormick, J. R., Su, E. P., Driks, A. & Losick, R. Growth and viability of Streptomyces coelicolor mutant for the cell division gene ftsZ. Mol. Microbiol. 14, 243–254 (1994).
Lechevalier, M. P. in Bergey's Manual of Systematic Bacteriology (eds Williams, S. T., Sharpe, M. E. & Holt, J. G.) 2405–2417 (Williams and Wilkins, Baltimore, 1989).
Vobis, G. in Bergey's Manual of Systematic Bacteriology (eds Williams, S. T., Sharpe, M. E. & Holt, J. G.) 2418–2450 (Williams and Wilkins, Baltimore, 1989).
Vobis, G. in The Prokaryotes (eds Balows, A., Truper, H. G., Dworkin, M., Harder, W. & Schleifer, K. H.) 1029–1060 (Springer, New York, 1992).
Parenti, F. & Coronelli, C. Members of the genus Actinoplanes and their antibiotics. Annu. Rev. Microbiol. 33, 389–411 (1979).
Lazzarini, A., Cavaletti, L., Toppo, G. & Marinelli, F. Rare genera of actinomycetes as potential producers of new antibiotics. Antonie Van Leeuwenhoek 78, 399–405 (2000).
Lechevalier, H. & Holbert, P. E. Electron microscopic observation of the sporangial structure of a strain of Actinoplanes. J. Bacteriol. 89, 217–222 (1965).
Lechevalier, H. A., Lechevalier, M. P. & Holbert, P. E. Electron microscopic observation of the sporangial structure of strains of Actinoplanaceae. J. Bacteriol. 92, 1228–1235 (1966). Together with reference 80, this paper provides a detailed ultrastructure-based description of sporangial development in Micromonosporaceae with comparisons to streptomycete spore development.
Stolp, H. & Starr, M. P. Bdellovibrio bacteriovorus gen. et sp. n., a predatory, ectoparasitic, and bacteriolytic microorganism. Antonie Van Leeuwenhoek 29, 217–248 (1963).
Starr, M. P. & Baigent, N. L. Parasitic interaction of Bdellovibrio bacteriovorus with other bacteria. J. Bacteriol. 91, 2006–2017 (1966).
Diedrich, D. L., Denny, C. F., Hashimoto, T. & Conti, S. F. Facultatively parasitic strain of Bdellovibrio bacteriovorus. J. Bacteriol. 101, 989–996 (1970).
Burnham, J. C., Hashimoto, T. & Conti, S. F. Ultrastructure and cell division of a facultatively parasitic strain of Bdellovibrio bacteriovorus. J. Bacteriol. 101, 997–1004 (1970).
Rendulic, S. et al. A predator unmasked: life cycle of Bdellovibrio bacteriovorus from a genomic perspective. Science 303, 689–692 (2004).
Cotter, T. W. & Thomashow, M. F. A conjugation procedure for Bdellovibrio bacteriovorus and its use to identify DNA sequences that enhance the plaque-forming ability of a spontaneous host-independent mutant. J. Bacteriol. 174, 6011–6017 (1992).
Ajithkumar, V. P. et al. A novel filamentous Bacillus sp., strain NAF001, forming endospores and budding cells. Microbiol. 147, 1415–1423 (2001).
Waterbury, J. & Stanier, R. Two unicellular cyanobacteria which reproduce by budding. Arch. Microbiol. 115, 249–257 (1977).
Staley, J. T. & Fuerst, J. A. in Bergey's Manual of Systematic Bacteriology (eds Staley, J. T., Bryant, M. P., Pfennig, N. & Holt, J. G.) 1890–1993 (Williams and Wilkins, Baltimore 1989).
McDonald, I. R. et al. A review of bacterial methyl halide degradation: biochemistry, genetics and molecular ecology. Environ. Microbiol. 4, 193–203 (2002).
Moore, R. L. The biology of Hyphomicrobium and other prosthecate, budding bacteria. Ann. Rev. Microbiol. 35, 567–594 (1981).
Ausmees, N. & Jacobs-Wagner, C. Spatial and temporal control of differentiation and cell cycle progression in Caulobacter crescentus. Annu. Rev. Microbiol. 57, 225–247 (2003).
Quardokus, E. M. & Brun, Y. V. Cell cycle timing and developmental checkpoints in Caulobacter crescentus. Curr. Opin. Microbiol. 6, 541–549 (2003).
Ausmees, N., Kuhn, J. R. & Jacobs-Wagner, C. The bacterial cytoskeleton: an intermediate filament-like function in cell shape. Cell 115, 705–713 (2003).
Nelson, W. J. Adaptation of core mechanisms to generate cell polarity. Nature 422, 766–774 (2003).
Moore, R. L. & Hirsch, P. Nuclear apparatus of Hyphomicrobium. J. Bacteriol. 116, 1447–1455 (1973).
Zerfas, P. M., Kessel, M., Quintero, E. J. & Weiner, R. M. Fine-structure evidence for cell membrane partitioning of the nucleoid and cytoplasm during bud formation in Hyphomonas species. J. Bacteriol. 179, 148–156 (1997). Remarkable electron micrographs showing the transit of vesicles through the Hyphomonas prostheca to the developing bud.
Brun, Y. V. & Janakiraman, R. in Prokaryotic Development (eds Brun, Y. V. & Shimkets, L. J.) 297–317 (American Society for Microbiology Press, Washington DC, 2000).
Bernal, A., Ear, U. & Kyrpides, N. Genomes onLine database (GOLD): a monitor of genome projects world-wide. Nucleic Acids Res. 29, 126–127 (2001).
I thank P. Levin and several anonymous reviewers for their helpful comments. I apologise to colleagues whose work, or favourite organism, has not been cited in this review owing to space constraints. Research in my laboratory is supported by the National Science Foundation.
The author declares no competing financial interests.
The highly organized chromosomal DNA of a bacterial cell.
Internal network of proteins that gives a eukaryotic cell its shape, facilitates its movement and provides a means of internal spatial organization.
A specialized dormant cell, that forms within some Gram-positive bacteria, and which is highly resistant to agents (such as heat, solvents and ultraviolet radiation) that would normally harm a vegetative cell.
Feeding on faeces.
A tapered protrusion of the segmented filamentous bacterial cell that firmly secures it to an epithelial cell that lines the host intestinal tract.
A low nutrient environment.
A cellular extension, also known as a stalk or hypha, which contains cytoplasm and is bound by the cell envelope of the organism.
About this article
Cite this article
Angert, E. Alternatives to binary fission in bacteria. Nat Rev Microbiol 3, 214–224 (2005). https://doi.org/10.1038/nrmicro1096
This article is cited by
Detection and characterization of rice orange leaf phytoplasma infection in rice and Recilia dorsalis
Phytopathology Research (2022)
Scientific Reports (2020)
Nature Reviews Microbiology (2019)
Recombination contributes to population diversification in the polyploid intestinal symbiont Epulopiscium sp. type B
The ISME Journal (2019)