A healthy bacterial cell begins its cell cycle, grows and divides quite rapidly — every 20 to 30 minutes — which may explain why bacteria can spread so quickly in contaminated food.
Cell division, the final stage of the bacterial cell cycle, involves a network of molecules to control the position of the division machinery, the divisome, at midcell. In E. coli, a bacterium that lives in our gut, the initial assembly of the division machinery requires three major proteins, FtsZ, FtsA and ZipA, and together these proteins form the proto-ring at midcell. In a recent minireview published in The Journal of Biological Chemistry, Ana Isabel Rico and colleagues from the Centro Nacional de Biotecnologia in Madrid describe the importance of these proteins in the formation, maturation, stabilization and function of the E. coli division machinery.
Firstly, the location of the division site needs to be determined. This occurs through two negative regulatory systems, nucleoid occlusion and the Min system, which inhibit the polymerization of FtsZ at undesired positions. This in turn blocks the assembly of the proto-ring at places that are not the midcell.
The FtsZ polymers need to be organized and stabilized at the division site. The exact arrangement of FtsZ polymers in the proto-ring is not completely known, although two models (ribbon and scattered) have been suggested. In addition, the assembly and stabilization of FtsZ polymers in the proto-ring are regulated by FtsZ-associated proteins known as Zap proteins.
|Encapsulation and polymerization of FtsZ inside permeable vesicles (A) and vesicle shrinkage and collapse induced by interaction of membrane bound ZipA with FtsZ polymers (B). Click on the image to see a larger version of it.
While FtsZ is a cytoplasmic protein, the other components of the proto-ring are associated with the inner membrane, and hence FtsA and ZipA act as anchors for the FtsZ polymers. A stable proto-ring is composed of FtsA and FtsZ polymers arranged in the correct orientation at the inner membrane. ZipA, a transmembrane protein, also provides a physical link of FtsZ to the membrane in either its monomeric or homodimeric form.
After identifying the location and organizing the proto-ring, this initial protein assemblage needs to mature prior to forming the septum. Firstly, preseptal peptidoglycan synthesis occurs to initiate transversal growth, leading to the production of the septum, and it has been shown that FtsZ, attached to the membrane by ZipA, is needed for this step. Secondly, proto-ring elements need to interact with late-assembling divisome proteins; hence, FtsZ interacts with FtsE, and FtsA interacts with FtsN.
The proto-ring is stabilized once the rest of the divisome proteins are recruited. Some of these proteins include FtsK, FtsEX, FtsQ, FtsB, FtsL, FtsW, FtsI and FtsN, clearly showing that the stabilization of the proto-ring of E.coli is not a simple process.
The membrane constricts, and the formation of the septum begins. It is believed that FtsZ is the driving force for the constriction, which seems to be exerted from the cytoplasm by pulling the envelope inward. Two models have been proposed: the bending or condensation of FtsZ polymers.
The proto-ring is vital for the initial phase of E. coli cell division, and the authors of this minireview summarize the stages and the divisome protein interactions required to form the septum. However, “a description of the detailed molecular mechanisms involved in septation” and “the connection between the biochemical properties of each divisome component” remain unresolved. Clearly, these and other questions still need to be explored, including what happens to the components of the proto-ring once the septum is closed. Key stages of assembling the E. coli proto-ring include the identification of the division site, the organization and stabilization of the structure, the maturation of the protein assemblage, and the formation of the septum. When the conditions are favorable, these stages can be repeated after 20 minutes.
Lesley Wassef (email@example.com) is a research associate in the Food Science and Rutgers Center for Lipid Research at Rutgers University.