Division site positioning in bacteria: one size does not fit all

Abstract

Spatial regulation of cell division in bacteria has been a focus of research for decades. It has been well studied in two model rod-shaped organisms, Escherichia coli and Bacillus subtilis, with the general belief that division site positioning occurs as a result of the combination of two negative regulatory systems, Min and nucleoid occlusion. These systems influence division by preventing the cytokinetic Z ring from forming anywhere other than midcell. However, evidence is accumulating for the existence of additional mechanisms that are involved in controlling Z ring positioning both in these organisms and in several other bacteria. In some cases the decision of where to divide is solved by variations on a common evolutionary theme, and in others completely different proteins and mechanisms are involved. Here we review the different ways bacteria solve the problem of finding the right place to divide. It appears that a one-size-fits-all model does not apply, and that individual species have adapted a division-site positioning mechanism that best suits their lifestyle, environmental niche and mode of growth to ensure equal partitioning of DNA for survival of the next generation.

Keywords: Z ring; bacterial cell division; cell division; division regulation; ftsZ; min system; nucleoid occlusion.

FIGURE 1

Spatial regulation of Z ring assembly in E. coli and B. subtilis. (A) The Min system and nucleoid occlusion (NO) inhibit Z ring formation at inappropriate sites. The Min proteins (blue) are concentrated to the cell poles, while the nucleoid (red) occupies the central region of the cell. The later stages of chromosome segregation result in a relief of nucleoid occlusion due to the removal of Noc/SlmA away from midcell, allowing Z ring formation at this site. (B) The “Ready-Set-Go” model proposes that identification of the division site is linked to the progress of DNA replication in B. subtilis, independently of both the Min system and nucleoid occlusion (Moriya et al., 2010). (i–iv) Progression of the initiation phase of DNA replication in B. subtilis, resulting in replisome assembly at oriC, promotes the maturation of a midcell site. This may occur due to the accumulation of a factor at midcell that activates FtsZ polymerization into a ring at this site (increasing darkness of green shading). (i) The binding of the early initiation protein DnaA to unwind the DNA at oriC starts midcell “potentiation.” Next, other early DNA replication initiation proteins, such as DnaB, bind this chromosomal region and increase midcell potentiation (light green area at midcell). (ii) DnaC helicase is then loaded, followed by PolC (the α-subunit of DNA polymerase III) and other replisome components, creating the replication fork at oriC. This further potentiates midcell (green area at midcell). (iii) Assembly of the remaining replisome components to complete initiation, ready for DNA synthesis, allows 100% potentiation of midcell (dark green area at midcell) for Z ring formation (red line). (iv) Midcell Z ring formation does not occur straight away since this requires ~70% of the chromosome to be replicated (Wu et al., 1995) to clear the bulk of the replicating DNA from midcell. (A) is reproduced from Monahan and Harry (2013) and (B) is adapted from Moriya et al. (2010), both with permission from Wiley Interscience.

FIGURE 2

Mechanisms for division site selection in different bacterial species. (A) In C. crescentus, Z ring positioning is controlled by the FtsZ inhibitor MipZ (purple). MipZ associates with the chromosome, and forms a gradient of decreasing concentration with distance from the cell pole (see text). In newborn cells with one chromosome, the MipZ gradient is established from a single pole, confining FtsZ (green) to the opposite pole. Chromosome replication and segregation establishes a bipolar MipZ gradient that dislodges FtsZ from the pole and restricts Z ring assembly to midcell. (B) In sporulating hyphae of S. coelicolor, Z ring assembly is positively regulated by the SsgB protein (dark blue), which localizes to division sites (via SsgA) then recruits FtsZ (green). SsgB remains associated with the Z ring. (C) In M. xanthus, PomZ (magenta) localizes to the cell center following chromosome segregation, then recruits FtsZ to form the Z ring (green). (D) S. aureus has been proposed to utilize specific peptidoglycan features in conjunction with nucleoid occlusion for division in three perpendicular planes. Double-headed arrow indicates the axis of chromosome segregation. The plane for septum formation is marked by the presence of the quarter rib. The axis of chromosome segregation is determined by the movement of the nucleoids to junctions of two previous division planes. To determine the next division plane, Staphylococcal cells may recognize the quarter rib feature via a direct receptor-ligand type interaction (Turner et al., 2010). The plane containing the quarter rib also has the longest circumference which could be used for recognition by the cell (Turner et al., 2010). Division plane selection might also be aided by establishing the axis of chromosome segregation toward the junctions between division planes (green circles). (E) In S. pneumoniae, division plane selection has been suggested to rely on the presence of equatorial rings for cell division in consecutive parallel planes (see text). Equatorial rings are present at the cell equator and mark the site for septal cell wall synthesis through recruitment of divisome components such as FtsZ. The equatorial rings are then duplicated and move apart, via the synthesis of new peripheral peptidoglycan, until both rings are located at the equators of the new daughter cells. New peripheral and septal peptidoglycan synthesis are highlighted in gray and blue, respectively. (F) N. gonorrhoeae cell division in alternating perpendicular planes. At the onset of cell division, two temporarily asymmetric daughter cells are generated which have a short and long axis (Pinho et al., 2013). This leads to the oscillation of the Min protein complex as well as chromosome segregation along the long axis, which is parallel to the septal plane (Pinho et al., 2013). Note that N. gonorrhoeae does not contain a Noc/SlmA homolog, but the presence of the replisome machinery around the DNA may negatively regulate divisome assembly around the DNA, analogous to the action of Noc (Ramirez-Arcos et al., 2002). Double-headed arrow indicates axis of chromosome segregation. (A) is reproduced from Monahan and Harry (2013) and (B,C) are adapted from Monahan and Harry (2013) with permission from Wiley Interscience.