The plasmid status of satellite bacteriophage P4

P4 is a natural phasmid (phage-plasmid) that exploits different modes of propagation in its host Escherichia coli. Extracellularly, P4 is a virion, with a tailed icosahedral head, which encapsidates the 11.6-kb-long double-stranded DNA genome. After infection of the E. coli host, P4 DNA can integrate into the bacterial chromosome and be maintained in a repressed state (lysogeny). Alternatively, P4 can replicate as a free DNA molecule; this leads to either the lytic cycle or the plasmid state, depending on the presence or absence of the genome of a helper phage P2 in the E. coli host. As a phage, P4 is thus a satellite of P2 phage, depending on the helper genes for all the morphogenetic functions, whereas for all its episomal functions (integration and immunity, multicopy plasmid replication) P4 is completely autonomous from the helper. Replication of P4 DNA depends on its alpha protein, a multifunctional polypeptide that exhibits primase and helicase activity and binds specifically the P4 origin. Replication starts from a unique point, ori1, and proceeds bidirectionally in a straight theta-type mode. P4 negatively regulates the plasmid copy number at several levels. An unusual mechanism of copy number control is based on protein-protein interaction: the P4-encoded Cnr protein interacts with the alpha gene product, inhibiting its replication potential. Furthermore, expression of the replication genes cnr and alpha is regulated in a complex way that involves modulation of promoter activity by positive and negative factors and multiple mechanisms of transcription elongation-termination control. Thus, the relatively small P4 genome encodes mostly regulatory functions, required for its propagation both as an episomal element and as a temperate satellite phage. Plasmids that, like P4, propagate horizontally via a specific transduction mechanism have also been found in the Archaea. The presence of P4-like prophages or cryptic prophages often associated with accessory bacterial functions attests to the contribution of satellite phages to bacterial evolution.