Cell division in Corynebacterineae

Abstract

Bacterial cells must coordinate a number of events during the cell cycle. Spatio-temporal regulation of bacterial cytokinesis is indispensable for the production of viable, genetically identical offspring. In many rod-shaped bacteria, precise midcell assembly of the division machinery relies on inhibitory systems such as Min and Noc. In rod-shaped Actinobacteria, for example Corynebacterium glutamicum and Mycobacterium tuberculosis, the divisome assembles in the proximity of the midcell region, however more spatial flexibility is observed compared to Escherichia coli and Bacillus subtilis. Actinobacteria represent a group of bacteria that spatially regulate cytokinesis in the absence of recognizable Min and Noc homologs. The key cell division steps in E. coli and B. subtilis have been subject to intensive study and are well-understood. In comparison, only a minimal set of positive and negative regulators of cytokinesis are known in Actinobacteria. Nonetheless, the timing of cytokinesis and the placement of the division septum is coordinated with growth as well as initiation of chromosome replication and segregation. We summarize here the current knowledge on cytokinesis and division site selection in the Actinobacteria suborder Corynebacterineae.

Keywords: Corynebacterium glutamicum; DivIVA; FtsZ; Mycobacterium tuberculosis; Par system; cell cycle; cell division; serine/threonine kinases.

Figure 1

Alignment of ParA proteins highlighting basic residues involved in DNA-binding. Surface exposed arginine residues have been shown to be involved in DNA-binding in B. subtilis Soj (Hester and Lutkenhaus, 2007). We have aligned sequence of different ParA/MinD proteins using ClustalW2. The alignment was rendered in ESPript (Gouet et al., 2003). Note that C. glutamicum ParA and PldP have the conserved positive charges (arrows) identified for DNA-binding in B. subtilis, while MinD lacks positive charges at these sites. Bsu, B. subtilis; Ccr, C. crescentus; Cgl, C. glutamicum; Mtu, M. tuberculosis; Mxa, M. xanthus; Tth, T. thermophilus.

Figure 2

Putative PknA phosphorylation sites on FtsZ. Shown is a homology model of C. glutamicum FtsZ. The residues phosphorylated by Ser/Thr protein kinases are shown in red and indicated. Residue T108 is involved in nucleotide binding/hydrolysis, T63 is at the interface of the FtsZ oligomerization domain. Residues S353 and T388 are located toward the C-terminal end. The C-terminal end is not depicted in this model.

Figure 3

Comparison of cell division in C. glutamicum and B. subtilis. (A) Directly after cell division, one cell pole contains a ParB-bound origin that is tethered at the old cell pole through interaction with the polar growth determinant DivIVA. At this stage of the cell cycle, we speculate that polar growth is asymmetric with the pole lacking a tethered origin (young pole) growing slower than origin bound pole (arrows). In B. subtilis, the post-divisional cell contains a centrally located nucleoid with the oriC and terC also found positioned at the midcell. (B) Initiation of chromosome replication gives rise to duplication of the oriC. In C. glutamicum, the newly duplicated oriC is bound by ParB, then ParA is recruited and the oriC is segregated to the opposite cell pole. FtsZ assembles into a Z-ring prior to complete segregation of the chromosome. The Z-ring does not always assemble precisely at midcell. The orphan ParA-like protein, PldP localizes to the division site, where it might function to spatially regulate cell division. In B. subtilis a centrally positioned replisome duplicates the chromosome. While the Min system protects the poles and Noc protects the chromosome from aberrant Z-ring assembly, some aspect of replication initiation positively influences midcell localization of the Z-ring (note that DivIVA is not part of the Min system here). Contrary to the asymmetric polar growth in C. glutamicum, B. subtilis grow at a uniform rate along the lateral axis (arrows). (C) In C. glutamicum, the sister origin is tethered at the cell pole by an interaction with DivIVA. This interaction then leads to an increase in growth from this pole (arrow). Polar growth, in addition with bulk chromosome segregation mechanisms, would aid in segregating the chromosomes. As the septum invaginates, DivIVA begins to localize at the site of division. In B. subtilis, the Min system moves from the cell poles to the invaginating septum. The midcell localized Min system prevents the divisome from reassembling near to an old division site.