Plasmid copy number control: an ever-growing story

Bacterial plasmids maintain their number of copies by negative regulatory s ystems that adjust the rate of replication per plasmid copy in response to fluctuations in the copy number. Three general classes of regulatory mechan isms have been studied in depth, namely those that involve directly repeate d sequences (iterons), those that use only antisense RNAs and those that us e a mechanism involving an antisense RNA in combination with a protein. The first class of control mechanism will not be discussed here. Within the se cond class (the most 'classical' one), exciting insights have been obtained on the molecular basis of the inhibition mechanism that prevents the forma tion of a long-range RNA structure (pseudoknot), which is an example of an elegant solution reached by some replicons to control their copy number. Am ong the third class, it is possible to distinguish between (i) cases in whi ch proteins play an auxiliary role; and (ii) cases in which transcriptional repressor proteins play a real regulatory role. This latter type of regula tion is relatively new and seems to be widespread among plasmids from Gramp ositive bacteria, at least for the rolling circle-replicating plasmids of t he pMV158 family and the theta-replicating plasmids of the lnc18 streptococ cal family.