Plasmid Incompatibility Is Determined by the Replicon

KEY CONCEPT
- Plasmids in a single compatibility group have origins that are regulated by a common control system.
The phenomenon of plasmid incompatibility is related to the regulation of plasmid copy number and segregation. A compatibility group is defined as a set of plasmids whose members are unable to coexist in the same bacterial cell. The reason for their incompatibility is that they cannot be distinguished from one another at some stage that is essential for plasmid maintenance. DNA replication and segregation are stages at which this may apply.
The negative control model for plasmid incompatibility follows the idea that copy number control is achieved by synthesizing a repressor that measures the concentration of origins. (Formally, this is the same as the titration model for regulating replication of the bacterial chromosome.)
The introduction of a new origin in the form of a second plasmid of the same compatibility group mimics the result of replication of the resident plasmid; two origins now are present. Thus, any further replication is prevented until after the two plasmids have been segregated to different cells to create the correct prereplication copy number, as illustrated in FIGURE 1.

FIGURE 1. Two plasmids are incompatible (they belong to the same compatibility group) if their origins cannot be distinguished at the stage of initiation. The same model could apply to segregation.
A similar effect would be produced if the system for segregating the products to daughter cells could not distinguish between two plasmids. For example, if two plasmids have the same cis-acting partition sites, competition between them would ensure that they would be segregated to different cells, and therefore could not survive in the same line.
The presence of a member of one compatibility group does not directly affect the survival of a plasmid belonging to a different group. Only one replicon of a given compatibility group (of a singlecopy plasmid) can be maintained in the bacterium, but it does not interact with replicons of other compatibility groups.

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