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  • Review Article
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Insights into the assembly and regulation of the bacterial divisome

Nature Reviews Microbiology volume 22, pages 33–45 (2024)Cite this article

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Abstract

The ability to split one cell into two is fundamental to all life, and many bacteria can accomplish this feat several times per hour with high accuracy. Most bacteria call on an ancient homologue of tubulin, called FtsZ, to localize and organize the cell division machinery, the divisome, into a ring-like structure at the cell midpoint. The divisome includes numerous other proteins, often including an actin homologue (FtsA), that interact with each other at the cytoplasmic membrane. Once assembled, the protein complexes that comprise the dynamic divisome coordinate membrane constriction with synthesis of a division septum, but only after overcoming checkpoints mediated by specialized protein–protein interactions. In this Review, we summarize the most recent evidence showing how the divisome proteins of Escherichia coli assemble at the cell midpoint, interact with each other and regulate activation of septum synthesis. We also briefly discuss the potential of divisome proteins as novel antibiotic targets.

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Fig. 1: Centring and organizing the divisome.
Fig. 2: Stages involved in the construction of the Escherichia coli divisome.
Fig. 3: FtsA oligomerization state regulates divisome activation.
Fig. 4: Divisome proteins build the septum in two tracks.
Fig. 5: Binding of a small-molecule inhibitor to the FtsZ interdomain cleft.

References

  1. Bi, E. & Lutkenhaus, J. FtsZ ring structure associated with division in Escherichia coli. Nature 354, 161–164 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Yang, X. et al. GTPase activity-coupled treadmilling of the bacterial tubulin FtsZ organizes septal cell wall synthesis. Science 355, 744–747 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bisson-Filho, A. W. et al. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science 355, 739–743 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. van Den Ent, F. & Löwe, J. Crystal structure of the cell division protein FtsA from Thermotoga maritima. EMBO J. 19, 5300–5307 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Pichoff, S. & Lutkenhaus, J. Unique and overlapping roles for ZipA and FtsA in septal ring assembly in Escherichia coli. EMBO J. 21, 685–693 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pichoff, S. & Lutkenhaus, J. Tethering the Z ring to the membrane through a conserved membrane targeting sequence in FtsA. Mol. Microbiol. 55, 1722–1734 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Hale, C. A. & de Boer, P. A. Direct binding of FtsZ to ZipA, an essential component of the septal ring structure that mediates cell division in E. coli. Cell 88, 175–185 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Rico, A. I., Krupka, M. & Vicente, M. In the beginning, Escherichia coli assembled the proto-ring: an initial phase of division. J. Biol. Chem. 288, 20830–20836 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Du, S., Henke, W., Pichoff, S. & Lutkenhaus, J. How FtsEX localizes to the Z ring and interacts with FtsA to regulate cell division. Mol. Microbiol. 112, 881–895 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Den Blaauwen, T., Buddelmeijer, N., Aarsman, M. E., Hameete, C. M. & Nanninga, N. Timing of FtsZ assembly in Escherichia coli. J. Bacteriol. 181, 5167–5175 (1999).

    Article  Google Scholar 

  11. Aarsman, M. E. et al. Maturation of the Escherichia coli divisome occurs in two steps. Mol. Microbiol. 55, 1631–1645 (2005). This study provides evidence that divisome assembly is regulated by some type of checkpoint.

    Article  CAS  PubMed  Google Scholar 

  12. Attaibi, M. & den Blaauwen, T. An updated model of the divisome: regulation of the septal peptidoglycan synthesis machinery by the divisome. Int. J. Mol. Sci. 23, 3537 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schmidt, K. L. et al. A predicted ABC transporter, FtsEX, is needed for cell division in Escherichia coli. J. Bacteriol. 186, 785–793 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Taguchi, A. et al. FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein. Nat. Microbiol. 4, 587–594 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Huang, K. H., Durand-Heredia, J. & Janakiraman, A. FtsZ ring stability: of bundles, tubules, crosslinks, and curves. J. Bacteriol. 195, 1859–1868 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Levin, P. A. & Janakiraman, A. Localization, assembly, and activation of the Escherichia coli cell division machinery. EcoSal 9, eESP00222021 (2021).

    Article  Google Scholar 

  17. Sun, Q. & Margolin, W. FtsZ dynamics during the cell division cycle of live Escherichia coli. J. Bacteriol. 180, 2050–2056 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rowlett, V. W. & Margolin, W. The Min system and other nucleoid-independent regulators of Z ring positioning. Front. Microbiol. 6, 478 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Schumacher, M. A. Bacterial nucleoid occlusion: multiple mechanisms for preventing chromosome bisection during cell division. Subcell. Biochem. 84, 267–298 (2017).

    Article  CAS  PubMed  Google Scholar 

  20. Bernhardt, T. G. & de Boer, P. A. SlmA, a nucleoid-associated, FtsZ-binding protein required for blocking septal ring assembly over chromosomes in E. coli. Mol. Cell 18, 555–564 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. de Boer, P. A. J., Crossley, R. E. & Rothfield, L. I. A division inhibitor and a topological specificity factor coded for by the minicell locus determine the proper placement of the division site in Escherichia coli. Cell 56, 641–649 (1989).

    Article  PubMed  Google Scholar 

  22. Lutkenhaus, J. & Sundaramoorthy, M. MinD and role of the deviant Walker A motif, dimerization and membrane binding in oscillation. Mol. Microbiol. 48, 295–303 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. de Boer, P. A. J., Crossley, R. E., Hand, A. R. & Rothfield, L. I. The MinD protein is a membrane ATPase required for the correct placement of the Escherichia coli division site. EMBO J. 10, 4371–4380 (1991).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hu, Z. & Lutkenhaus, J. Topological regulation of cell division in E. coli. Spatiotemporal oscillation of MinD requires stimulation of its ATPase by MinE and phospholipid. Mol. Cell 7, 1337–1343 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Raskin, D. M. & de Boer, P. A. The MinE ring: an FtsZ-independent cell structure required for selection of the correct division site in E. coli. Cell 91, 685–694 (1997).

    Article  CAS  PubMed  Google Scholar 

  26. Huang, K. C., Meir, Y. & Wingreen, N. S. Dynamic structures in Escherichia coli: spontaneous formation of MinE rings and MinD polar zones. Proc. Natl Acad. Sci. USA 100, 12724–12728 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Glock, P. et al. Stationary patterns in a two-protein reaction–diffusion system. ACS Synth. Biol. 8, 148–157 (2019).

    Article  CAS  PubMed  Google Scholar 

  29. Loose, M., Fischer-Friedrich, E., Ries, J., Kruse, K. & Schwille, P. Spatial regulators for bacterial cell division self-organize into surface waves in vitro. Science 320, 789–792 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. Ramm, B. et al. The MinDE system is a generic spatial cue for membrane protein distribution in vitro. Nat. Commun. 9, 3942 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Godino, E., Doerr, A. & Danelon, C. Min waves without MinC can pattern FtsA-anchored FtsZ filaments on model membranes. Commun. Biol. 5, 675 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hu, Z. & Lutkenhaus, J. Analysis of MinC reveals two independent domains involved in interaction with MinD and FtsZ. J. Bacteriol. 182, 3965–3971 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Raskin, D. M. & de Boer, P. A. Rapid pole-to-pole oscillation of a protein required for directing division to the middle of Escherichia coli. Proc. Natl Acad. Sci. USA 96, 4971–4976 (1999). This seminal study demonstrates how the Min system spatially restricts Z-ring formation to midcell in Escherichia coli.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Thanedar, S. & Margolin, W. FtsZ exhibits rapid movement and oscillation waves in helix-like patterns in Escherichia coli. Curr. Biol. 14, 1167–1173 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bisicchia, P., Arumugam, S., Schwille, P. & Sherratt, D. MinC, MinD, and MinE drive counter-oscillation of early-cell-division proteins prior to Escherichia coli septum formation. mBio 4, e00856-13 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Corbin, B. D., Yu, X.-C. & Margolin, W. Exploring intracellular space: function of the Min system in round-shaped Escherichia coli. EMBO J. 21, 1988–2008 (2002).

    Article  Google Scholar 

  37. Schweizer, J. et al. Geometry sensing by self-organized protein patterns. Proc. Natl Acad. Sci. USA 109, 15283–15288 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Juarez, J. R. & Margolin, W. Changes in the Min oscillation pattern before and after cell birth. J. Bacteriol. 192, 4134–4142 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ghosal, D., Trambaiolo, D., Amos, L. A. & Löwe, J. MinCD cell division proteins form alternating copolymeric cytomotive filaments. Nat. Commun. 5, 5341 (2014).

    Article  CAS  PubMed  Google Scholar 

  40. Conti, J., Viola, M. G. & Camberg, J. L. The bacterial cell division regulators MinD and MinC form polymers in the presence of nucleotide. FEBS Lett. 589, 201–206 (2015).

    Article  CAS  PubMed  Google Scholar 

  41. Huang, H. et al. The cell division protein MinD from Pseudomonas aeruginosa dominates the assembly of the MinC–MinD copolymers. J. Biol. Chem. 293, 7786–7795 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wang, N., Zhang, T., Du, S., Zhou, Y. & Chen, Y. How do MinC–D copolymers act on Z-ring localization regulation? A new model of Bacillus subtilis Min system. Front. Microbiol. 13, 841171 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Park, K.-T., Du, S. & Lutkenhaus, J. MinC/MinD copolymers are not required for Min function. Mol. Microbiol. 98, 895–909 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tonthat, N. K. et al. Molecular mechanism by which the nucleoid occlusion factor, SlmA, keeps cytokinesis in check. EMBO J. 30, 154–164 (2011).

    Article  CAS  PubMed  Google Scholar 

  45. Du, S. & Lutkenhaus, J. SlmA antagonism of FtsZ assembly employs a two-pronged mechanism like MinCD. PLoS Genet. 10, e1004460 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Schumacher, M. A. & Zeng, W. Structures of the nucleoid occlusion protein SlmA bound to DNA and the C-terminal domain of the cytoskeletal protein FtsZ. Proc. Natl Acad. Sci. USA 113, 4988–4993 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cho, H., McManus, H. R., Dove, S. L. & Bernhardt, T. G. Nucleoid occlusion factor SlmA is a DNA-activated FtsZ polymerization antagonist. Proc. Natl Acad. Sci. USA 108, 3773–3778 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tonthat, N. K. et al. SlmA forms a higher-order structure on DNA that inhibits cytokinetic Z-ring formation over the nucleoid. Proc. Natl Acad. Sci. USA 110, 10586–10591 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 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).

    Article  CAS  PubMed  Google Scholar 

  50. Adams, D. W., Wu, L. J. & Errington, J. Nucleoid occlusion protein Noc recruits DNA to the bacterial cell membrane. EMBO J. 34, 491–501 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yu, Y. et al. The division defect of a Bacillus subtilis minD noc double mutant can be suppressed by Spx-dependent and Spx-independent mechanisms. J. Bacteriol. 203, e0024921 (2021).

    Article  PubMed  Google Scholar 

  52. Monterroso, B. et al. Bacterial FtsZ protein forms phase-separated condensates with its nucleoid-associated inhibitor SlmA. EMBO Rep. 20, e45946 (2019). This study reports that bacterial cell division proteins can undergo liquid–liquid phase separation.

    Article  PubMed  Google Scholar 

  53. Babl, L., Merino-Salomón, A., Kanwa, N. & Schwille, P. Membrane mediated phase separation of the bacterial nucleoid occlusion protein Noc. Sci. Rep. 12, 17949 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Paccione, G. et al. Lipid surfaces and glutamate anions enhance formation of dynamic biomolecular condensates containing bacterial cell division protein FtsZ and its DNA-bound regulator SlmA. Biochemistry 15, 2482–2489 (2022).

    Article  Google Scholar 

  55. Yu, J., Liu, Y., Yin, H. & Chang, Z. Regrowth-delay body as a bacterial subcellular structure marking multidrug-tolerant persisters. Cell Discov. 5, 8 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Robles-Ramos, M. Á. et al. Assembly of bacterial cell division protein FtsZ into dynamic biomolecular condensates. Biochim. Biophys. Acta Mol. Cell Res. 1868, 118986 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Harms, A., Maisonneuve, E. & Gerdes, K. Mechanisms of bacterial persistence during stress and antibiotic exposure. Science 354, aaf4268 (2016).

    Article  PubMed  Google Scholar 

  58. Ramm, B. et al. Biomolecular condensate drives polymerization and bundling of the bacterial tubulin FtsZ to regulate cell division. Nat. Commun. 14, 3825 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hoang, Y., Azaldegui, C. A., Ghalmi, M., Biteen, J. S. & Vecchiarelli, A. G. An experimental framework to assess biomolecular condensates in bacteria. Preprint at bioRxiv https://doi.org/10.1101/2023.03.22.533878 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Osawa, M. & Erickson, H. P. Liposome division by a simple bacterial division machinery. Proc. Natl Acad. Sci. USA 110, 11000–11004 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Godino, E. et al. De novo synthesized Min proteins drive oscillatory liposome deformation and regulate FtsA–FtsZ cytoskeletal patterns. Nat. Commun. 10, 4969 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Yoshida, A., Kohyama, S., Fujiwara, K., Nishikawa, S. & Doi, N. Regulation of spatiotemporal patterning in artificial cells by a defined protein expression system. Chem. Sci. 10, 11064–11072 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Furusato, T. et al. De novo synthesis of basal bacterial cell division proteins FtsZ, FtsA, and ZipA inside giant vesicles. ACS Synth. Biol. 7, 953–961 (2018).

    Article  CAS  PubMed  Google Scholar 

  64. Godino, E. et al. Cell-free biogenesis of bacterial division proto-rings that can constrict liposomes. Commun. Biol. 3, 539 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kohyama, S., Merino-Salomón, A. & Schwille, P. In vitro assembly, positioning and contraction of a division ring in minimal cells. Nat. Commun. 13, 6098 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Godino, E. & Danelon, C. Gene-directed FtsZ ring assembly generates constricted liposomes with stable membrane necks. Adv. Biol. 7, e2200172 (2023). Together with Kohyama et al. (2022), this study makes an important advance in reconstituting the divisome by using the MinC–MinD–MinE complex to corral FtsZ polymers, tethered by FtsA, to the midpoint of lipid vesicles and constrict them.

    Article  Google Scholar 

  67. Espeli, O. et al. A MatP–divisome interaction coordinates chromosome segregation with cell division in E. coli. EMBO J. 31, 3198–3211 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Galli, E. & Gerdes, K. Spatial resolution of two bacterial cell division proteins: ZapA recruits ZapB to the inner face of the Z-ring. Mol. Microbiol. 76, 1514–1526 (2010).

    Article  CAS  PubMed  Google Scholar 

  69. Mannik, J. & Bailey, M. W. Spatial coordination between chromosomes and cell division proteins in Escherichia coli. Front. Microbiol. 6, 306 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Buss, J. et al. A multi-layered protein network stabilizes the Escherichia coli FtsZ-ring and modulates constriction dynamics. PLoS Genet. 11, e1005128 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Coltharp, C., Buss, J., Plumer, T. M. & Xiao, J. Defining the rate-limiting processes of bacterial cytokinesis. Proc. Natl Acad. Sci. USA 113, E1044–E1053 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Buss, J. A., Peters, N. T., Xiao, J. & Bernhardt, T. G. ZapA and ZapB form an FtsZ-independent structure at midcell. Mol. Microbiol. 104, 652–663 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Schumacher, D. et al. The PomXYZ proteins self-organize on the bacterial nucleoid to stimulate cell division. Dev. Cell 41, 299–314.e13 (2017).

    Article  CAS  PubMed  Google Scholar 

  74. Fleurie, A. et al. MapZ marks the division sites and positions FtsZ rings in Streptococcus pneumoniae. Nature 516, 259–262 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Willemse, J., Borst, J. W., de Waal, E., Bisseling, T. & van Wezel, G. P. Positive control of cell division: FtsZ is recruited by SsgB during sporulation of Streptomyces. Genes Dev. 25, 89–99 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Briggs, N. S., Bruce, K. E., Naskar, S., Winkler, M. E. & Roper, D. I. The pneumococcal divisome: dynamic control of Streptococcus pneumoniae cell division. Front. Microbiol. 12, 737396 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Buddelmeijer, N. & Beckwith, J. A complex of the Escherichia coli cell division proteins FtsL, FtsB and FtsQ forms independently of its localization to the septal region. Mol. Microbiol. 52, 1315–1327 (2004).

    Article  CAS  PubMed  Google Scholar 

  78. Khadria, A. S. & Senes, A. The transmembrane domains of the bacterial cell division proteins FtsB and FtsL form a stable high-order oligomer. Biochemistry 52, 7542–7550 (2013).

    Article  CAS  PubMed  Google Scholar 

  79. Chen, J. C., Weiss, D. S., Ghigo, J. M. & Beckwith, J. Septal localization of FtsQ, an essential cell division protein in Escherichia coli. J. Bacteriol. 181, 521–530 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hale, C. A. & de Boer, P. A. Recruitment of ZipA to the septal ring of Escherichia coli is dependent on FtsZ and independent of FtsA. J. Bacteriol. 181, 167–176 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Liu, G., Draper, G. C. & Donachie, W. D. FtsK is a bifunctional protein involved in cell division and chromosome localization in Escherichia coli. Mol. Microbiol. 29, 893–903 (1998).

    Article  CAS  PubMed  Google Scholar 

  82. Aussel, L. et al. FtsK is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases. Cell 108, 195–205 (2002).

    Article  CAS  PubMed  Google Scholar 

  83. Dubarry, N., Possoz, C. & Barre, F.-X. Multiple regions along the Escherichia coli FtsK protein are implicated in cell division. Mol. Microbiol. 78, 1088–1100 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Saaki, T. N. V. et al. SepF supports the recruitment of the DNA translocase SftA to the Z-ring. Mol. Microbiol. 117, 1263–1274 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Berezuk, A. M., Goodyear, M. & Khursigara, C. M. Site-directed fluorescence labeling reveals a revised N-terminal membrane topology and functional periplasmic residues in the Escherichia coli cell division protein FtsK. J. Biol. Chem. 289, 23287–23301 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Draper, G. C., McLennan, N., Begg, K., Masters, M. & Donachie, W. D. Only the N-terminal domain of FtsK functions in cell division. J. Bacteriol. 180, 4621–4627 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wang, L. & Lutkenhaus, J. FtsK is an essential cell division protein that is localized to the septum and induced as part of the SOS response. Mol. Microbiol. 29, 731–740 (1998).

    Article  CAS  PubMed  Google Scholar 

  88. Yu, X.-C., Tran, A. H., Sun, Q. & Margolin, W. Localization of cell division protein FtsK to the Escherichia coli septum and identification of a potential N-terminal targeting domain. J. Bacteriol. 180, 1296–1304 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kureisaite-Ciziene, D. et al. Structural analysis of the interaction between the bacterial cell division proteins FtsQ and FtsB. mBio 9, e01346-18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Choi, Y. et al. Structural insights into the FtsQ/FtsB/FtsL complex, a key component of the divisome. Sci. Rep. 8, 18061 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Marmont, L. S. & Bernhardt, T. G. A conserved subcomplex within the bacterial cytokinetic ring activates cell wall synthesis by the FtsW–FtsI synthase. Proc. Natl Acad. Sci. USA 117, 23879–23885 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Park, K.-T., Pichoff, S., Du, S. & Lutkenhaus, J. FtsA acts through FtsW to promote cell wall synthesis during cell division in Escherichia coli. Proc. Natl Acad. Sci. USA 118, e2107210118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Britton, B. M. et al. Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism. Preprint at bioRxiv https://doi.org/10.1101/2022.11.27.518129 (2022).

    Article  Google Scholar 

  94. Kashammer, L. et al. Divisome core complex in bacterial cell division revealed by cryo-EM. Nat. Microbiol. 8, 1149–1159 (2022). This important cryo-electron-microscopy study solves the structure of the FtsQ–FtsL–FtsB–FtsW–FtsI complex of Pseudomonas aeruginosa, at 3.7 Å resolution, validating previous genetic studies that suggested that a direct FtsL–FtsI interaction in the periplasm is crucial for activation of septum synthesis.

    Article  Google Scholar 

  95. Berezuk, A. M., Roach, E. J., Seidel, L., Lo, R. Y. & Khursigara, C. M. FtsA G50E mutant suppresses the essential requirement for FtsK during bacterial cell division in Escherichia coli. Can. J. Microbiol. 66, 313–327 (2020).

    Article  CAS  PubMed  Google Scholar 

  96. Busiek, K. K., Eraso, J. M., Wang, Y. & Margolin, W. The early divisome protein FtsA interacts directly through its 1c subdomain with the cytoplasmic domain of the late divisome protein FtsN. J. Bacteriol. 194, 1989–2000 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Busiek, K. K. & Margolin, W. A role for FtsA in SPOR-independent localization of the essential Escherichia coli cell division protein FtsN. Mol. Microbiol. 92, 1212–1226 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Pichoff, S., Du, S. & Lutkenhaus, J. The bypass of ZipA by overexpression of FtsN requires a previously unknown conserved FtsN motif essential for FtsA–FtsN interaction supporting a model in which FtsA monomers recruit late cell division proteins to the Z ring. Mol. Microbiol. 95, 971–987 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Wissel, M. C. & Weiss, D. S. Genetic analysis of the cell division protein FtsI (PBP3): amino acid substitutions that impair septal localization of FtsI and recruitment of FtsN. J. Bacteriol. 186, 490–502 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Gerding, M. A. et al. Self-enhanced accumulation of FtsN at division sites and roles for other proteins with a SPOR domain (DamX, DedD, and RlpA) in Escherichia coli cell constriction. J. Bacteriol. 191, 7383–7401 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yahashiri, A., Jorgenson, M. A. & Weiss, D. S. The SPOR domain, a widely conserved peptidoglycan binding domain that targets proteins to the site of cell division. J. Bacteriol. 199, e00118-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Yahashiri, A., Jorgenson, M. A. & Weiss, D. S. Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan strands that lack stem peptides. Proc. Natl Acad. Sci. USA 112, 11347–11352 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Perez, A. J. et al. Movement dynamics of divisome proteins and PBP2x:FtsW in cells of Streptococcus pneumoniae. Proc. Natl Acad. Sci. USA 116, 3211–3220 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. McCausland, J. W. et al. Treadmilling FtsZ polymers drive the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism. Nat. Commun. 12, 609 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Monteiro, J. M. et al. Peptidoglycan synthesis drives an FtsZ-treadmilling-independent step of cytokinesis. Nature 554, 528–532 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Whitley, K. D. et al. FtsZ treadmilling is essential for Z-ring condensation and septal constriction initiation in Bacillus subtilis cell division. Nat. Commun. 12, 2448 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Lyu, Z., Coltharp, C., Yang, X. & Xiao, J. Influence of FtsZ GTPase activity and concentration on nanoscale Z-ring structure in vivo revealed by three-dimensional superresolution imaging. Biopolymers 105, 725–734 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Söderström, B. et al. Coordinated disassembly of the divisome complex in Escherichia coli. Mol. Microbiol. 101, 425–438 (2016).

    Article  PubMed  Google Scholar 

  109. Silber, N., Mayer, C., Matos de Opitz, C. L. & Sass, P. Progression of the late-stage divisome is unaffected by the depletion of the cytoplasmic FtsZ pool. Commun. Biol. 4, 270 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Corbin Goodman, L. C. & Erickson, H. P. FtsZ at mid-cell is essential in Escherichia coli until the late stage of constriction. Microbiology 168, 001194 (2022).

    Article  Google Scholar 

  111. Söderström, B., Chan, H., Shilling, P. J., Skoglund, U. & Daley, D. O. Spatial separation of FtsZ and FtsN during cell division. Mol. Microbiol. 107, 387–401 (2017).

    Article  PubMed  Google Scholar 

  112. Mannik, J., Walker, B. E. & Mannik, J. Cell cycle-dependent regulation of FtsZ in Escherichia coli in slow growth conditions. Mol. Microbiol. 110, 1030–1044 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Cameron, T. A., Vega, D. E., Yu, C., Xiao, H. & Margolin, W. ZipA uses a two-pronged FtsZ-binding mechanism necessary for cell division. mBio 12, e0252921 (2021).

    Article  PubMed  Google Scholar 

  114. Geissler, B. & Margolin, W. Evidence for functional overlap among multiple bacterial cell division proteins: compensating for the loss of FtsK. Mol. Microbiol. 58, 596–612 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Geissler, B., Elraheb, D. & Margolin, W. A gain of function mutation in ftsA bypasses the requirement for the essential cell division gene zipA in Escherichia coli. Proc. Natl Acad. Sci. USA 100, 4197–4202 (2003). This study reports landmark evidence that the divisome can be regulated by variations in FtsA.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Geissler, B., Shiomi, D. & Margolin, W. The ftsA* gain-of-function allele of Escherichia coli and its effects on the stability and dynamics of the Z ring. Microbiology 153, 814–825 (2007).

    Article  CAS  PubMed  Google Scholar 

  117. Pichoff, S., Shen, B., Sullivan, B. & Lutkenhaus, J. FtsA mutants impaired for self-interaction bypass ZipA suggesting a model in which FtsA’s self-interaction competes with its ability to recruit downstream division proteins. Mol. Microbiol. 83, 151–167 (2012).

    Article  CAS  PubMed  Google Scholar 

  118. Herricks, J. R., Nguyen, D. & Margolin, W. A thermosensitive defect in the ATP binding pocket of FtsA can be suppressed by allosteric changes in the dimer interface. Mol. Microbiol. 94, 713–727 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bernard, C. S., Sadasivam, M., Shiomi, D. & Margolin, W. An altered FtsA can compensate for the loss of essential cell division protein FtsN in Escherichia coli. Mol. Microbiol. 64, 1289–1305 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Mingorance, J., Rico, A. I. & Gomez-Puertas, P. Bacterial morphogenes. In Molecules In Time And Space. Bacterial Shape, Division And Phylogeny (eds Vicente, M., Tamames, J., Valencia, A. & Mingorance, J.) (Springer, 2004).

  121. Pazos, M. et al. Z-ring membrane anchors associate with cell wall synthases to initiate bacterial cell division. Nat. Commun. 9, 5090 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Krupka, M. et al. Escherichia coli FtsA forms lipid-bound minirings that antagonize lateral interactions between FtsZ protofilaments. Nat. Commun. 8, 15957 (2017). This paper reveals that FtsA forms mini-rings on lipid membranes in vitro and that hypermorphic FtsA* variants disrupt these mini-rings and promote bundling of tethered FtsZ protofilaments.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Schoenemann, K. M. et al. Gain-of-function variants of FtsA form diverse oligomeric structures on lipids and enhance FtsZ protofilament bundling. Mol. Microbiol. 109, 676–693 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Nierhaus, T. et al. Bacterial divisome protein FtsA forms curved antiparallel double filaments when binding to FtsN. Nat. Microbiol. 7, 1686–1701 (2022). This key structural study demonstrates that binding of the cytoplasmic domain of FtsN to FtsA can convert FtsA mini-rings into curved double-stranded filaments that are oriented in antiparallel.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Radler, P. et al. In vitro reconstitution of Escherichia coli divisome activation. Nat. Commun. 13, 2635 (2022). This analysis of fluorescently labelled proteins on supported lipid bilayers shows that FtsA* promotes FtsZ treadmilling through higher membrane packing density and FtsN facilitates FtsA–FtsA interactions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Conti, J., Viola, M. G. & Camberg, J. L. FtsA reshapes membrane architecture and remodels the Z-ring in Escherichia coli. Mol. Microbiol. 107, 558–576 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Liu, B., Persons, L., Lee, L. & de Boer, P. A. Roles for both FtsA and the FtsBLQ subcomplex in FtsN-stimulated cell constriction in Escherichia coli. Mol. Microbiol. 95, 945–970 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Dai, K., Xu, Y. & Lutkenhaus, J. Cloning and characterization of ftsN, an essential cell division gene in Escherichia coli isolated as a multicopy suppressor of ftsA12(Ts). J. Bacteriol. 175, 3790–3797 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Goehring, N. W., Robichon, C. & Beckwith, J. A role for the non-essential N-terminus of FtsN in divisome assembly. J. Bacteriol. 189, 646–649 (2007).

    Article  CAS  PubMed  Google Scholar 

  130. Pichoff, S., Du, S. & Lutkenhaus, J. Disruption of divisome assembly rescued by FtsN–FtsA interaction in Escherichia coli. Proc. Natl Acad. Sci. USA 115, E6855–E6862 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Männik, J., Pichoff, S., Lutkenhaus, J. & Männik, J. Cell cycle-dependent recruitment of FtsN to the divisome in Escherichia coli. mBio 13, e0201722 (2022).

    Article  PubMed  Google Scholar 

  132. Karuppiah, V. & Derrick, J. P. Structure of the PilM-PilN inner membrane type IV pilus biogenesis complex from Thermus thermophilus. J. Biol. Chem. 286, 24434–24442 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Llontop, E. E. et al. The PilB–PilZ–FimX regulatory complex of the type IV pilus from Xanthomonas citri. PLoS Pathog. 17, e1009808 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Chang, Y.-W. et al. Architecture of the type IVa pilus machine. Science 351, aad2001 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  135. Du, S., Pichoff, S. & Lutkenhaus, J. FtsEX acts on FtsA to regulate divisome assembly and activity. Proc. Natl Acad. Sci. USA 113, E5052–E5061 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Reddy, M. Role of FtsEX in cell division of Escherichia coli: viability of ftsEX mutants is dependent on functional SufI or high osmotic strength. J. Bacteriol. 189, 98–108 (2007).

    Article  CAS  PubMed  Google Scholar 

  137. Vega, D. E. & Margolin, W. Direct interaction between the two Z ring membrane anchors FtsA and ZipA. J. Bacteriol. 201, e00579-18 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Yang, D. C. et al. An ATP-binding cassette transporter-like complex governs cell-wall hydrolysis at the bacterial cytokinetic ring. Proc. Natl Acad. Sci. USA 108, E1052–E1060 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Du, S., Pichoff, S. & Lutkenhaus, J. Roles of ATP hydrolysis by FtsEX and interaction with FtsA in regulation of septal peptidoglycan synthesis and hydrolysis. mBio 11, e01247-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Navarro, P. P. et al. Cell wall synthesis and remodelling dynamics determine division site architecture and cell shape in Escherichia coli. Nat. Microbiol. 7, 1621–1634 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Szwedziak, P., Wang, Q., Bharat, T. A. M., Tsim, M. & Löwe, J. Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division. eLife 3, e04601 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Shiomi, D. & Margolin, W. Dimerization or oligomerization of the actin-like FtsA protein enhances the integrity of the cytokinetic Z ring. Mol. Microbiol. 66, 1396–1415 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Buske, P. J. & Levin, P. A. A flexible C-terminal linker is required for proper FtsZ assembly in vitro and cytokinetic ring formation in vivo. Mol. Microbiol. 89, 249–263 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Huecas, S. et al. Self-organization of FtsZ polymers in solution reveals spacer role of the disordered C-terminal tail. Biophys. J. 113, 1831–1844 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Barrows, J. M., Sundararajan, K., Bhargava, A. & Goley, E. D. FtsA regulates Z-ring morphology and cell wall metabolism in an FtsZ C-terminal linker-dependent manner in Caulobacter crescentus. J. Bacteriol. 202, e00693-19 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  146. Squyres, G. R. et al. Single-molecule imaging reveals that Z-ring condensation is essential for cell division in Bacillus subtilis. Nat. Microbiol. 6, 553–562 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Haeusser, D. P., Rowlett, V. W. & Margolin, W. A mutation in Escherichia coli ftsZ bypasses the requirement for the essential division gene zipA and confers resistance to FtsZ assembly inhibitors by stabilizing protofilament bundling. Mol. Microbiol. 97, 988–1005 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Krupka, M., Sobrinos-Sanguino, M., Jimenez, M., Rivas, G. & Margolin, W. Escherichia coli ZipA organizes FtsZ polymers into dynamic ring-like protofilament structures. mBio 9, e1008–e1018 (2018).

    Article  Google Scholar 

  149. Jaiswal, R. et al. E93R substitution of Escherichia coli FtsZ induces bundling of protofilaments, reduces GTPase activity, and impairs bacterial cytokinesis. J. Biol. Chem. 285, 31796–31805 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Karimova, G., Dautin, N. & Ladant, D. Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis. J. Bacteriol. 187, 2233–2243 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. van den Ent, F., Izoré, T., Bharat, T. A., Johnson, C. M. & Löwe, J. Bacterial actin MreB forms antiparallel double filaments. eLife 3, e02634 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Hussain, S. et al. MreB filaments align along greatest principal membrane curvature to orient cell wall synthesis. eLife 7, e32471 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Szwedziak, P. & Löwe, J. Do the divisome and elongasome share a common evolutionary past? Curr. Opin. Microbiol. 16, 745–751 (2013).

    Article  CAS  PubMed  Google Scholar 

  154. Begg, K. J. et al. The balance between different peptidoglycan precursors determines whether Escherichia coli cells will elongate or divide. J. Bacteriol. 172, 6697–6703 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Lleo, M. M., Canepari, P. & Satta, G. Bacterial cell shape regulation: testing of additional predictions unique to the two-competing-sites model for peptidoglycan assembly and isolation of conditional rod-shaped mutants from some wild-type cocci. J. Bacteriol. 172, 3758–3771 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Tsang, M. J. & Bernhardt, T. G. A role for the FtsQLB complex in cytokinetic ring activation revealed by an ftsL allele that accelerates division. Mol. Microbiol. 95, 925–944 (2015). Together with Liu et al. (2015), this study shows that the FtsB–FtsL–FtsQ complex has a key regulatory role in activating the divisome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Park, K.-T., Du, S. & Lutkenhaus, J. Essential role for FtsL in activation of septal peptidoglycan synthesis. mBio 11, e03012-20 (2020). This study provides strong genetic evidence for the key role of FtsL in activating FtsW–FtsI.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Li, Y. et al. Genetic analysis of the septal peptidoglycan synthase FtsWI complex supports a conserved activation mechanism for SEDS–bPBP complexes. PLoS Genet. 17, e1009366 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Lariviere, P. J. et al. An essential regulator of bacterial division links FtsZ to cell wall synthase activation. Curr. Biol. 29, 1460–1470.e4 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Kiekebusch, D., Michie, K. A., Essen, L. O., Löwe, J. & Thanbichler, M. Localized dimerization and nucleoid binding drive gradient formation by the bacterial cell division inhibitor MipZ. Mol. Cell 46, 245–259 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Mahone, C. R. et al. Integration of cell wall synthesis activation and chromosome segregation during cell division in Caulobacter. Preprint at bioRxiv https://doi.org/10.1101/2022.11.05.515301 (2022).

    Article  Google Scholar 

  162. Gallay, C. et al. CcrZ is a pneumococcal spatiotemporal cell cycle regulator that interacts with FtsZ and controls DNA replication by modulating the activity of DnaA. Nat. Microbiol. 6, 1175–1187 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Loose, M. & Mitchison, T. J. The bacterial cell division proteins FtsA and FtsZ self-organize into dynamic cytoskeletal patterns. Nat. Cell Biol. 16, 38–46 (2014).

    Article  CAS  PubMed  Google Scholar 

  164. Baranova, N. et al. Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments and cell division proteins. Nat. Microbiol. 5, 407–417 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Lyu, Z. et al. FtsN maintains active septal cell wall synthesis by forming a processive complex with the septum-specific peptidoglycan synthases in E. coli. Nat. Commun. 13, 5751 (2022). This study complements recent structural studies showing that FtsN binds to and moves with the septum synthesis complex.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Khanna, K., Lopez-Garrido, J., Sugie, J., Pogliano, K. & Villa, E. Asymmetric localization of the cell division machinery during Bacillus subtilis sporulation. eLife 10, e62204 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Cameron, T. A. & Margolin, W. Construction and characterization of functional FtsA sandwich fusions for studies of FtsA localization and dynamics during Escherichia coli cell division. J. Bacteriol. 205, e0037322 (2022).

    Article  Google Scholar 

  168. Pende, N. et al. SepF is the FtsZ anchor in archaea, with features of an ancestral cell division system. Nat. Commun. 12, 3214 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Duman, R. et al. Structural and genetic analyses reveal the protein SepF as a new membrane anchor for the Z ring. Proc. Natl Acad. Sci. USA 110, E4601–E4610 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Dey, S. & Zhou, H.-X. Membrane tethering of SepF, a membrane anchor for the Mycobacterium tuberculosis Z-ring. J. Mol. Biol. 434, 167817 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Ishikawa, S., Kawai, Y., Hiramatsu, K., Kuwano, M. & Ogasawara, N. A new FtsZ-interacting protein, YlmF, complements the activity of FtsA during progression of cell division in Bacillus subtilis. Mol. Microbiol. 60, 1364–1380 (2006).

    Article  CAS  PubMed  Google Scholar 

  172. Wenzel, M. et al. Control of septum thickness by the curvature of SepF polymers. Proc. Natl Acad. Sci. USA 118, e2002635118 (2021).

    Article  CAS  PubMed  Google Scholar 

  173. Levin, P. A., Kurtser, I. G. & Grossman, A. D. Identification and characterization of a negative regulator of FtsZ ring formation in Bacillus subtilis. Proc. Natl Acad. Sci. USA 96, 9642–9647 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Perez, A. J. et al. FtsZ-ring regulation and cell division are mediated by essential EzrA and accessory proteins ZapA and ZapJ in Streptococcus pneumoniae. Front. Microbiol. 12, 780864 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Datta, P., Dasgupta, A., Bhakta, S. & Basu, J. Interaction between FtsZ and FtsW of Mycobacterium tuberculosis. J. Biol. Chem. 277, 24983–24987 (2002).

    Article  CAS  PubMed  Google Scholar 

  176. Smrt, S. T., Escobar, C. A., Dey, S., Cross, T. A. & Xhou, H. X. An Arg/Ala-rich helix in the N-terminal region of M. tuberculosis FtsQ is a potential membrane anchor of the Z-ring. Commun. Biol. 6, 311 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Yang, X. et al. A two-track model for the spatiotemporal coordination of bacterial septal cell wall synthesis revealed by single-molecule imaging of FtsW. Nat. Microbiol. 6, 584–593 (2021). The analysis in this paper provides landmark evidence that divisome proteins engaged in septum synthesis move much more slowly along the membrane than FtsZ treadmilling filaments.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Bisson-Filho, A. W. et al. FtsZ filament capping by MciZ, a developmental regulator of bacterial division. Proc. Natl Acad. Sci. USA 112, E2130–E2138 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Du, S., Pichoff, S., Kruse, K. & Lutkenhaus, J. FtsZ filaments have the opposite kinetic polarity of microtubules. Proc. Natl Acad. Sci. USA 115, 10768–10773 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Adams, D. W., Wu, L. J., Czaplewski, L. G. & Errington, J. Multiple effects of benzamide antibiotics on FtsZ function. Mol. Microbiol. 80, 68–84 (2011).

    Article  CAS  PubMed  Google Scholar 

  181. Straniero, V. et al. Computational design and development of benzodioxane-benzamides as potent inhibitors of FtsZ by exploring the hydrophobic subpocket. Antibiotics 10, 442 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Du, R.-L. et al. Gossypol acetate: a natural polyphenol derivative with antimicrobial activities against the essential cell division protein FtsZ. Front. Microbiol. 13, 1080308 (2022).

    Article  PubMed  Google Scholar 

  183. Paulussen, F. M. et al. Covalent proteomimetic inhibitor of the bacterial FtsQB divisome complex. J. Am. Chem. Soc. 144, 15303–15313 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank the National Institutes of Health (grant R35GM131705) for funding their research.

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    Todd A. Cameron & William Margolin

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Cameron, T.A., Margolin, W. Insights into the assembly and regulation of the bacterial divisome. Nat Rev Microbiol 22, 33–45 (2024). https://doi.org/10.1038/s41579-023-00942-x

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