Filamentous Bacteriophages: Biology and Applications

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Abstract Filamentous bacteriophages (family Inoviridae) contain a circular single‐stranded DNA genome packaged into long filaments. They do not lyse bacteria; instead, they are secreted into the environment without killing the host. Well‐studied Escherichia coli ‐infecting Ff phages (f1, fd or M13) replicate episomally; however, most filamentous phage in other organisms are ‘lysogenic’. Filamentous phage diversity and range were vastly underestimated until 2019, when bioinformatic analyses of prokaryotic genomes and shot‐gun metagenomes discovered 10,295 novel filamentous phage‐derived prophages in nearly all bacterial phyla and in some archaea. Some filamentous phages enhance the virulence of their host organisms, the most striking example being the CTXφ of Vibrio cholerae , which encodes cholera toxin. E. coli Ff phages are the workhorse of phage display technology, whose most notable ‘products’ are therapeutic recombinant antibodies. Ff phages are also being used as a particulate vaccine carriers or diagnostic particles and in nanotechnology as templates for assembly of nanostructures. Key Concepts Filamentous bacteriophages are long filaments (6–7 nm × >500 nm) that contain a single‐stranded circular DNA genome. Filamentous bacteriophages replicate via a rolling‐circle mechanism, one strand at a time. Filamentous bacteriophages do not lyse the cells; they are released by secretion, using a dedicated filamentous phage assembly secretion system. Filamentous phage secretion‐assembly requires the proton‐motive force and ATP. Some filamentous phages replicate exclusively as episomes, while others also integrate their genomes into the host chromosome, forming a lysogen. Induction of the lysogen does not result in cell lysis. Ff filamentous phages of E. coli (f1, M13 and fd) have been used interchangeably as vectors and helper phages in DNA sequencing, as a protein display platform in phage display technology and as a template for assembly of nanostructures in nanotechnology. Filamentous phages are widely distributed among bacteria and archaea and are present in virtually all major microbial ecological niches. Recent genome and metagenome analyses discovered 10,295 filamentous phages within bacterial and archaeal genomes.