Partition-mediated incompatibility of bacterial plasmids

Abstract

Stuart Austin* and Kurt Nordsttimt * Laboratory of Chromosome Biology BRI-Basic Research Program NCI-Frederick Cancer Research Facility Frederick, Maryland 21701 f Department of Microbiology Biomedical Center University of Uppsala Uppsala Sweden Two plasmid species that are unable to coexist stably in a growing population of bacteria are termed incompatible; incompatible plasmids are found to be genetically related. Novick and Hoppensteadt (1978) pointed out that this could be explained if such plasmids shared specific deter- minants that caused them to be selected at random from a free pool at a stage essential for plasmid maintenance, such as replication or partition to daughter cells. The role of choice for replication in incompatibility is well established. All bacterial plasmids replicate randomly over the whole cell cycle, and copies are selected as tem- plates at random from a plasmid pool. Hence, some cop- ies may not replicate at all, whereas others may be repli- cated more than once during a single cell cycle. Pairs of plasmids containing the same determinants are chosen at random with respect to each other, leading to distortions in their relative copy numbers; eventually, pure lines con- taining only one plasmid type are formed. The partition of plasmid copies to daughter cells must also play an important role in incompatibility. Distribution of plasmid copies to daughter cells by random diffusion, the mechanism apparently adopted by most high copy number plasmids, would exaggerate distortions in relative copy number and hasten the production of pure lines. Even in a hypothetical case where replication determi- nants are shared but make no contribution to incompatibil- ity, a random assortment of copies to daughter cells would result in the production of pure lines (Nordstrom et al., 1981). However, incompatibility studies of plasmids that have nonrandom, active systems for partition are the most revealing. Plasmid Partition Naturally occurring bacterial plasmids are very stably maintained. This is particularly remarkable in the case of low copy number plasmids such as Pl, F, and the incFl/ plasmids (Rl and NRl) in Escherichia coli. They normally confer no selective advantage to their host. Yet, despite copy numbers as low as two per dividing cell, loss fre- quencies approximate one per million cell division events. In addition to efficient replication controls, this degree of stability requires a combination of several plasmid- encoded functions, including recombination systems that resolve plasmid multimers and functions that can kill a proportion of any plasmid-free cells that arise (reviewed in Nordstrom and Austin, 1989). However, the primary mech-