More than just a phase: the search for membraneless organelles in the bacterial cytoplasm

  • Elio A. Abbondanzieri
  • Anne S. Meyer


The bacterial cytoplasm, once thought to be a relatively undifferentiated reaction medium, has now been recognized to have extensive microstructure. This microstructure includes bacterial microcompartments, inclusion bodies, granules, and even some membrane-bound vesicles. Several recent papers suggest that bacteria may also organize their cytoplasm using an additional mechanism: phase-separated membraneless organelles, a strategy commonly used by eukaryotes. Phase-separated membraneless organelles such as Cajal bodies, the nucleolus, and stress granules allow proteins to become concentrated in sub-compartments of eukaryotic cells without being surrounded by a barrier to diffusion. In this review, we summarize the known structural organization of the bacterial cytoplasm and discuss the recent evidence that phase-separated membraneless organelles might also play a role in bacterial systems. We specifically focus on bacterial ribonucleoprotein complexes and two different protein components of the bacterial nucleoid that may have the ability to form subcellular partitions within bacteria cells.


Bacterial nucleoid Liquid–liquid phase separation Subcellular organelles Membraneless compartment Cellular organization Dps 



  1. Azam TA, Ishihama A (1999) Twelve species of the nucleoid-associated protein from Escherichia coli. Sequence recognition specificity DNA binding affinity. J Biol Chem 274:33105–33113CrossRefGoogle Scholar
  2. Azam TA, Iwata A, Nishimura A, Ueda S, Ishihama A (1999) Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. J Bacteriol 181:6361–6370Google Scholar
  3. Banani SF, Lee HO, Hyman AA, Rosen MK (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 18:285–298. CrossRefGoogle Scholar
  4. Bernhardt TG, de Boer PA (2005) SlmA, a nucleoid-associated, FtsZ binding protein required for blocking septal ring assembly over chromosomes in E. coli. Mol cell 18:555–564. CrossRefGoogle Scholar
  5. Boeynaems S et al (2018) Protein phase separation: a new phase in cell biology. Trends Cell Biol 28:420–435. CrossRefGoogle Scholar
  6. Brangwynne CP et al (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324:1729–1732. CrossRefGoogle Scholar
  7. Cornejo E, Abreu N, Komeili A (2014) Compartmentalization and organelle formation in bacteria. Curr Opin Cell Biol 26:132–138. CrossRefGoogle Scholar
  8. Cox B, Tuite M (2018) The life of [PSI]. Curr Genet 64:1–8. CrossRefGoogle Scholar
  9. Enenkel C (2018) The paradox of proteasome granules. Curr Genet 64:137–140. CrossRefGoogle Scholar
  10. Feric M et al (2016) Coexisting liquid phases underlie. Nucleolar Subcompart Cell 165:1686–1697. CrossRefGoogle Scholar
  11. Frenkiel-Krispin D et al (2001) Regulated phase transitions of bacterial chromatin: a non-enzymatic pathway for generic DNA protection. Embo J 20:1184–1191. CrossRefGoogle Scholar
  12. Gomes E, Shorter J (2018) The molecular language of membraneless organelles. J Biol Chem. Google Scholar
  13. Hansma HG (2017) Better than membranes at the origin of life? Life. Google Scholar
  14. Janissen R et al (2018) Global DNA compaction in stationary-phase bacteria does not affect transcription. Cell 174:1188–1199 e1114. CrossRefGoogle Scholar
  15. Jun S, Mulder B (2006) Entropy-driven spatial organization of highly confined polymers: lessons for the bacterial chromosome. Proc Natl Acad Sci USA 103:12388–12393. CrossRefGoogle Scholar
  16. Karas VO, Westerlaken I, Meyer AS (2015) The DNA-binding protein from starved cells (Dps) utilizes dual functions to defend cells against multiple stresses. J Bacteriol 197:3206–3215. CrossRefGoogle Scholar
  17. Kerfeld CA, Aussignargues C, Zarzycki J, Cai F, Sutter M (2018) Bacterial microcompartments. Nat Rev Microbiol 16:277–290. CrossRefGoogle Scholar
  18. Kim J, Yoshimura SH, Hizume K, Ohniwa RL, Ishihama A, Takeyasu K (2004) Fundamental structural units of the Escherichia coli nucleoid revealed by atomic force microscopy. Nucleic Acids Res 32:1982–1992. CrossRefGoogle Scholar
  19. Langdon EM, Gladfelter AS (2018) A new lens for RNA localization liquid–liquid phase separation. Annu Rev Microbiol 72:255–271. CrossRefGoogle Scholar
  20. Lutkenhaus J (2007) Assembly dynamics of the bacterial MinCDE system and spatial regulation of the Z ring. Annu Rev Biochem 76:539–562. CrossRefGoogle Scholar
  21. Molliex A et al (2015) Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163:123–133. CrossRefGoogle Scholar
  22. Monterroso B, Zorrilla S, Sobrinos-Sanguino M, Keating CD, Rivas G (2016) Microenvironments created by liquid–liquid phase transition control the dynamic distribution of bacterial division FtsZ protein. Sci Rep 6:35140. CrossRefGoogle Scholar
  23. Monterroso B, Zorrilla S, Sobrinos-Sanguino M, Robles-Ramos MA, López-Álvarez M, Keating CD, Rivas G (2018) Bacterial division FtsZ forms liquid condensates with nucleoid-associated Z-ring inhibitor. SlmA bioRxiv Google Scholar
  24. Nevo-Dinur K, Nussbaum-Shochat A, Ben-Yehuda S, Amster-Choder O (2011) Translation-independent localization of mRNA in E. coli. Science 331:1081–1084. CrossRefGoogle Scholar
  25. Nott TJ et al (2015) Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol cell 57:936–947. CrossRefGoogle Scholar
  26. Odijk T (1998) Osmotic compaction of supercoiled DNA into a bacterial nucleoid. Biophys Chem 73:23–29CrossRefGoogle Scholar
  27. Pederson T (2011) The nucleolus. Cold Spring Harb Perspect Biol. Google Scholar
  28. Pelletier J et al (2012) Physical manipulation of the Escherichia coli chromosome reveals its soft nature. Proc Natl Acad Sci USA 109:E2649–E2656. CrossRefGoogle Scholar
  29. Racki LR, Tocheva EI, Dieterle MG, Sullivan MC, Jensen GJ, Newman DK (2017) Polyphosphate granule biogenesis is temporally and functionally tied to cell cycle exit during starvation in Pseudomonas aeruginosa. Proc Natl Acad Sci USA 114:E2440–E2449. CrossRefGoogle Scholar
  30. Rinas U, Garcia-Fruitos E, Corchero JL, Vazquez E, Seras-Franzoso J, Villaverde A (2017) Bacterial inclusion bodies: discovering their better half. Trends Biochem Sci 42:726–737. CrossRefGoogle Scholar
  31. Russell JH, Keiler KC (2009) Subcellular localization of a bacterial regulatory RNA. Proc Natl Acad Sci USA 106:16405–16409. CrossRefGoogle Scholar
  32. Ryzhova TA et al (2018) Screening for amyloid proteins in the yeast proteome. Curr Genet 64:469–478. CrossRefGoogle Scholar
  33. Shapiro L, McAdams HH, Losick R (2009) Why and how bacteria. localize proteins. Science 326:1225–1228. CrossRefGoogle Scholar
  34. Simpson-Lavy K, Kupiec M (2018) A reversible liquid drop aggregation controls glucose response in yeast. Curr Genet 64:785–788. CrossRefGoogle Scholar
  35. Strom AR, Emelyanov AV, Mir M, Fyodorov DV, Darzacq X, Karpen GH (2017) Phase separation drives heterochromatin domain formation. Nature 547:241–245. CrossRefGoogle Scholar
  36. Sutter M et al (2008) Structural basis of enzyme encapsulation into a bacterial nanocompartment. Nat Struct Mol Biol 15:939–947. CrossRefGoogle Scholar
  37. Valkenburg JA, Woldringh CL (1984) Phase separation between nucleoid and cytoplasm in Escherichia coli as defined by immersive refractometry. J Bacteriol 160:1151–1157Google Scholar
  38. Vtyurina NN, Dulin D, Docter MW, Meyer AS, Dekker NH, Abbondanzieri EA (2016) Hysteresis in DNA compaction by Dps is described by an Ising model. Proc Natl Acad Sci USA 113:4982–4987. CrossRefGoogle Scholar
  39. Wang W, Li GW, Chen C, Xie XS, Zhuang X (2011) Chromosome organization by a nucleoid-associated protein in live bacteria. Science 333:1445–1449. CrossRefGoogle Scholar
  40. Wang X, Montero Llopis P, Rudner DZ (2013) Organization and segregation of bacterial chromosomes. Nat Rev Genet 14:191–203. CrossRefGoogle Scholar
  41. Wisniewski BT, Sharma J, Legan ER, Paulson E, Merrill SJ, Manogaran AL (2018) Toxicity and infectivity: insights from de novo prion formation. Curr Genet 64:117–123. CrossRefGoogle Scholar
  42. Wolf SG, Frenkiel D, Arad T, Finkel SE, Kolter R, Minsky A (1999) DNA protection by stress-induced biocrystallization. Nature 400:83–85CrossRefGoogle Scholar
  43. Yuan AH, Hochschild A (2017) A bacterial global regulator forms a prion. Science 355:198–201. CrossRefGoogle Scholar
  44. Zhang P, Khursigara CM, Hartnell LM, Subramaniam S (2007) Direct visualization of Escherichia coli chemotaxis receptor arrays using cryo-electron microscopy. Proc Natl Acad Sci USA 104:3777–3781. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiologyUniversity of RochesterRochesterUSA

Personalised recommendations