Bacterial Nucleoid Occlusion: Multiple Mechanisms for Preventing Chromosome Bisection During Cell Division

Abstract

In most bacteria cell division is driven by the prokaryotic tubulin homolog, FtsZ, which forms the cytokinetic Z ring. Cell survival demands both the spatial and temporal accuracy of this process to ensure that equal progeny are produced with intact genomes. While mechanisms preventing septum formation at the cell poles have been known for decades, the means by which the bacterial nucleoid is spared from bisection during cell division, called nucleoid exclusion (NO), have only recently been deduced. The NO theory was originally posited decades ago based on the key observation that the cell division machinery appeared to be inhibited from forming near the bacterial nucleoid. However, what might drive the NO process was unclear. Within the last 10 years specific proteins have been identified as important mediators of NO. Arguably the best studied NO mechanisms are those employed by the Escherichia coli SlmA and Bacillus subtilis Noc proteins. Both proteins bind specific DNA sequences within selected chromosomal regions to act as timing devices. However, Noc and SlmA contain completely different structural folds and utilize distinct NO mechanisms. Recent studies have identified additional processes and factors that participate in preventing nucleoid septation during cell division. These combined data show multiple levels of redundancy as well as a striking diversity of mechanisms have evolved to protect cells against catastrophic bisection of the nucleoid. Here we discuss these recent findings with particular emphasis on what is known about the molecular underpinnings of specific NO machinery and processes.

The Nucleoid Occlusion Protein SlmA Binds to Lipid Membranes

“…6B). Assembly of these FtsZ units would be under the control of the antagonist, in line with the general thought that to be effective, the negative regulation of FtsZ assembly by SlmA should be exerted not only in the cytoplasm but also next to the membrane (6,7). Inhibition of FtsZ polymerization is obviously crucial to counteract FtsZ ring formation prior to the start of cell division, but it is still required at other times to prevent aberrant ring formation by the majority of cellular FtsZ that is present outside the central ring (20).…”

“…The formation of higher-order SlmA assemblies once on the membrane, promoted by low salt, remains as a possible explanation for the enhanced binding avidity, which would emerge from several transient, probably weak, contacts between SlmA molecules at high local density and the lipid surface. This kind of multivalent interaction appears recurrently in the SlmA interaction network (7). Thus, SlmA targets two low-affinity sites within an FtsZ monomer (10), and stabilization of the overall complexes is achieved through contacts with multiple FtsZ subunits (18) arranged in filaments in the presence of GTP or in shorter oligomers in its absence.…”

“…It is widely accepted that the blockage of FtsZ ring assembly around the nucleoid by SlmA is not limited to the cytoplasm but should also occur at noncentral regions of the membrane (6,7,9,10). Such restrictions would reinforce the inhibition by other antagonists, like the Min system, which acts specifically at the membrane near the cell poles (11,12).…”

Stable Regulation of Cell Cycle Events in Mycobacteria: Insights From Inherently Heterogeneous Bacterial Populations

“…Wild type M. smegmatis cells divide at the central surface wave trough while cells deficient in chromosome partitioning can divide at off-center wave troughs, indicating a regulatory role for chromosome segregation in division site selection ( Eskandarian et al, 2017 ). Mycobacteria lack homologues of defined nucleoid occlusion systems (Noc proteins) and minicell (Min) proteins used by other bacteria to prevent chromosome splicing during cell division ( Wu and Errington, 2011 ; Monahan et al, 2014 ; Schumacher, 2017 ). Despite the lack of known nucleoid occlusion proteins, M. smegmatis cells exhibit a clear relationship between asymmetric chromosome positioning and asymmetric division placement ( Eskandarian et al, 2017 ; Logsdon et al, 2017 ) ( Figure 1B ).…”

Assembly of bacterial cell division protein FtsZ into dynamic biomolecular condensates

“…There have been relatively few studies dealing with condensates involving bacterial proteins (Abbondanzieri & Meyer, 2019;Al-Husini et al, 2018;Heinkel et al, 2019;Ladouceur et al, 2020;Wang et al, 2019). Among them, we recently described condensates (Monterroso et al, 2019) involving FtsZ, a key protein whose polymers organize into a dynamic ring-like structure required for bacterial division (Haeusser & Margolin, 2016), and SlmA, a DNA-binding protein that blocks FtsZ rings assembly over nucleoids in E. coli through direct interaction with FtsZ (Mannik & Bailey, 2015;Schumacher, 2017). On the basis of this finding, we proposed that biomolecular condensation may play a role in the regulation of bacterial division, through the modulation of nucleoid occlusion by SlmA (Monterroso et al, 2019).…”