Control of the bacterial cell cycle by cytoplasmic growth

For free-living single-celled organisms, it can be assumed that it is their success in acquiring resources and converting them into cytoplasm that controls the timing of their cell cycles. Cytoplasm is the sink for the bulk of the environmental resources. It must be the case that this type of control must operate in dilute cultures under adequate nutrition in a constant environment. It follows that there ought to be mechanisms that measure or count the cell's biomass or some component of the cytoplasm to measure their growth success. Besides sensing their biomass, they need to know when a certain value of the cell size has been achieved. When this critical state has been achieved, the cell needs to have an all-or-none trigger that either initiates chromosome replication, the completion of cell replication, cell division, or the process of separating sister cells physiologically or physically. Any of these four different stages, in principle, may be the one triggered in response to cell growth in different species of microorganisms. Alternatively, multiple triggers at different cell sizes may be activated at different cell cycle stages. Although initiation of chromosome replication has been believed to be the event triggered in Escherichia coli, this probably is not generally the case and other control mechanisms may act in other prokaryotes. How the increase in cell biomass is self-assessed and used to carry out critical cell cycle events is not understood in any case. This deficiency in our knowledge of microbial cell physiology is grave. The factor that probably has prevented the elucidation of the mechanisms in any organism is that enzymatic processes deal with concentrations, and a cell cycle trigger must respond to the total amount of material present in a cell. This article discusses the theoretically possible classes of mechanisms for the cell to respond when it has achieved its appropriate critical size. These breakdown into three groups: those mechanisms that assess the total amount of biomass or some special subcellular component, and those that measure the ratio of one component to another component where their two syntheses are differently controlled by cell physiology and morphology, and a third group with some specialized mechanisms.