Plasmid Segregation: Birds of a Feather Try Not To Flock Together

Abstract

Bacterial plasmids are extrachromosomal genetic elements having copy numbers ranging from one to a few thousand. The maintenance of plasmids in bacterial cells is dependent upon factors and processes that control their replication, selection, copy number, and segregation. Segregation of low-copy-number plasmids is generally dependent upon plasmid-encoded cytoskeletal elements that act as partitioning proteins (4). Inactivation of these proteins results in plasmid instability and loss (4). Past studies of segregation of the low-copy-number P1 plasmid (1 to 2 copies per chromosome) in Escherichia coli showed them to preferentially localize to the midcell or cell quarter position, depending upon their copy numbers and the cell division phase of the host (10). However, those studies were carried out on dividing cells with 2 copies of the plasmid, which is ideal for studying segregation—one copy is segregated to each daughter cell when the mother cell undergoes cell division. However, real-life scenarios could be far from ideal. In this issue, Sengupta and colleagues from the Austin group report their recent studies of P1 plasmid partitioning under more natural) conditions (14a). In their paper, they show that multiple copies of the low-copy-number P1 plasmid exist within the same cell in significant numbers, which is contrary to our present understanding. Using powerful cell biology tools and thoughtful studies that followed individual plasmid foci over extended periods, they discovered patterns that did not emerge in earlier time-averaged studies. They observed rampant chaotic behavior of plasmids. Their studies address how P1 plasmids segregate when they exist in more than the ideal copy number. Their data question the notion that sister plasmids are always paired and located at fixed positions within a cell and that segregation simply ensures the movement of sister plasmids to different daughter cells. The random pairings and diffusion of plasmid copies within a cell reported by Sengupta et al. (14a) invoke the possibility of random assortment of daughter plasmids (sisters and nonsisters) during cell division. Quite significantly, they show the existence of a self-correcting mechanism that places the copies of plasmids apart from each other and at more or less equal distances from each other when they exist within the same cell. Further investigations of the precise behavior of the P1 partitioning proteins at different growth rates and identification of hitherto unknown components will be crucial for deciphering the mechanistic basis for the dynamic self-correcting mechanism reported for the P1 plasmid by the Austin group. Due to the similarities in localization patterns of multicopy and high-copy-number plasmids that have been investigated so far (Fig. ​(Fig.1A)1A) (13, 16), it will not be surprising if the self-correcting mechanism for plasmid localization reported here for the P1 plasmid proves to be widespread. FIG. 1. Focus formation by plasmids. (A) Focus formation is not unique to low-copy-number plasmids. Multicopy and high-copy-number plasmids have been shown to assemble foci consisting of clusters of several plasmid molecules. The foci formed from clusters of ...