“Background Bacteriophages of the Leviviridae family are s


“Background Bacteriophages of the Leviviridae HMPL-504 nmr family are small viruses that infect several genera of Gram-negative bacteria. They have linear, positive-sense, single-stranded RNA genomes about 3500 – 4200 nucleotides in length that encode only four proteins. All Leviviridae phages have three genes in common – maturation, coat and replicase [1]. The replicase cistron encodes the catalytic subunit of the RNA-dependent RNA polymerase complex, which is assembled together with several bacterial

PI3K inhibitor proteins [2, 3] and replicates phage RNA. The coat protein forms dimers, 90 of which assemble in a T=3 icosahedral capsid about 27 nm in diameter and encapsidate the genome [4]. A single copy of the maturation protein binds to phage RNA [5] and gets incorporated into learn more capsids along with it. It is required for infectivity of the virions – the maturation protein binds to bacterial pili, then leaves the capsid and enters the cell as an RNA-protein complex [6]. Many of the Leviviridae phages are divided in two genera – leviviruses and alloleviviruses. The major distinction of alloleviviruses is

the presence of a minor coat protein A1 in their capsid which is produced by ribosomal read-through of a leaky termination codon of the coat gene [7]. The other difference is that the maturation protein of alloleviviruses also triggers cell lysis [8, 9], whereas leviviruses encode a dedicated small lysis polypeptide for this purpose [10–12]. The ssRNA phages that infect Escherichia coli cells by adsorbing to F plasmid-coded pili were the first isolates of the Leviviridae family [13, 14], and to date these “male-specific” phages, with type species MS2 and Qβ, have been the most Thiamet G intensively studied and best characterized of this family. However, the F plasmid is just one of the many conjugative plasmids that are present in nature. These plasmids are often highly divergent from F and are most often grouped according to their mutual compatibility. In Enterobacteriaceae, the conjugative plasmids form more than 20 different incompatibility (Inc) groups which are denoted by capital Latin letters [15]. All these plasmids

encode conjugative pili, but the pilin subunits often share no similarity. Several ssRNA phages specific for conjugative pili other than that of plasmid F have been discovered. Phage PRR1 [16] which adsorbs specifically to IncP plasmid-encoded pili was the first such example, and later other phages specific for Inc group C [17], D [18], H [19, 20], I [21], M [22] and T [23] plasmids followed. Phages PRR1, C-1 (IncC-specific) and Hgal1 (IncH-specific) have been sequenced [24, 25] and phage PRR1 capsids have also been crystallized [26], but no research has been done on the other plasmid-specific phages since their isolation. The IncM plasmid-specific RNA phage M [22] was isolated from sewage in Pretoria, South Africa in the beginning of the 1980s.

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