Autographiviridae

Autographiviridae
Virus classification
(unranked):	Virus
Realm:	Duplodnaviria
Kingdom:	Heunggongvirae
Phylum:	Uroviricota
Class:	Caudoviricetes
Order:	Caudovirales
Family:	Autographiviridae
Genera
	see text
Synonyms
	T7 supergroup;

Autographiviridae is a family of viruses in the order Caudovirales. Bacteria serve as natural hosts. There are 373 species in this family, assigned to 9 subfamilies and 133 genera.^[1]^[2]

History

Since the 1990s, the term "T7 supergroup" has been coined for the expanding group of bacteriophages related to coliphage T7, as members of the family Podoviridae. Enterobacteriaceae phages SP6 and K1-5 were the first to be considered as an estranged subgroup of the "T7 supergroup".^[3] Pseudomonas phage phiKMV also shared commonalities at the genome organizational level. As such, based on the available morphological and proteomic data, this clade of viruses was established as a subfamily of the family Podoviridae. The subfamily was later raised to the level of family in 2019.^[4]

Applications

Therapeutic Antibiotic Use

Some experiments suggest that Autographiviridae bacteriophages show promise in regulating and stifling the growth of infectious bacteria, like Klebsiella pneumoniae, in humans.^[5] Infectious bacteria like K. pneumoniae have increasingly become more resistant to traditional antibiotics. Some bacteria are even resistant to multiple antibiotics and antibacterial drugs.^[6] This problem prompted researchers to look towards other possible regulators of bacterial growth, like Autographiviridae bacteriophages.^[5] This type of treatment is referred to as phage therapy. Phage therapy is effective against drug-resistant bacteria because bacteriophages are naturally inclined to infect and kill specific bacteria.^[7]

For the past two decades, studying phage therapy has grown in popularity with major research centers opening up in the United States, Poland, Georgia, and Belgium. In turn, many biotechnology companies have shifted their focus to phage therapy, with some like Armata Pharmaceuticals completely dedicating themselves to combating the problem of antibiotic resistance.^[8]

Autographiviridae has also been used in combination with existing antibiotics to effective results. A recent study showed that Autographiviridae combined with antibiotic medication Tigecycline can effectively combat skin and soft tissue infections associated with Acinetobacter baumannii, a bacterium that previously showed resistance to multiple drugs.^[9]

However, phage therapy does pose some potential drawbacks. Antibiotics work by targeting a key part bacterial structure or by impeding a bacterial metabolic function. Because many bacteria have similar metabolic processes and physical structures, an antibiotic could be effective against many different bacteria. Phages on the other hand are much more specific to a single bacteria. This means that scientists would have to put in more work to perfect a phage therapy that only works against one bacteria. Also, some clinical studies involving phage therapy have resulted in low to moderate efficacy rates and in a huge variation of results for different patients.^[10]

Autographiviridae and other lytic phages lyse host bacteria through a process that begins with adsorption.^[11] Once Autographiviridae is adsorbed on the cell surface of the host bacteria, the enzyme located in its tail structure can penetrate the host bacteria’s peptidoglycan layer and inner membrane, where it releases genetic material into the interior of the bacteria. When the phage genetic material is integrated with the bacterial host genes, it will replicate to form a new progeny phage with bacteriolytic ability. The infected bacteria are finally lysed and the progeny phages released post-lysis continue to proliferate and lyse surrounding host bacteria.^[12]

Autographiviridae in Phage Cocktail Formulation

“Phage cocktails” are a form of phage therapy that involves employing at least two phages to target a single bacterial strain,^[13] creating a form of therapy with greater ‘depth.’ Phage cocktails are an effective substitute for antibiotics as they create a broader host range and delay the development of phage resistance in bacteria.^[14] Phage cocktails are most commonly used to combat infections caused by Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli.^[15]

Clinical practices have employed phage cocktails to prevent bacterial biofilm formation, which is one of the greatest challenges in the healthcare industry. A recent study showed that formulated phage cocktails that included Autographiviridae under the now-abolished family classification Podoviridae, effectively reduced the growth of Klebsiella pneumoniae.^[13]^[11]

Etymology

The name of this family, termed Autographiviridae, refers to the “auto-graphein” or “self-transcribing” phages which encode their own (single subunit) RNA polymerase, a common characteristic among its members.^{[citation needed]}

Structure

Viruses in Autographiviridae are non-enveloped, with icosahedral and Head-tail geometries, and T=7 symmetry. The diameter is around 60 nm. Genomes are linear, around 40-42kb in length.^[1]

Life cycle

Viral replication is cytoplasmic. DNA templated transcription is the method of transcription. The virus exits the host cell by lysis, and holin/endolysin/spanin proteins. Bacteria serve as the natural host. Transmission routes are passive diffusion.^[1]

Basis for taxonomy

The former family of Podoviridae, which contained many of the viruses that are now classified under Autographiviridae, was defined based on morphology and the presence of short noncontractile tails.^[16] The Podoviridae family, along with Myoviridae and Siphoviridae families, were abolished for being polyphyletic, meaning that viruses under a single family derived from more than one common ancestor and are thus not suitable for placing in the same taxa. However, these terms (Podoviridae, Myoviridae, and Siphoviridae) are still used to refer to the distinct morphological features of certain bacteriophages.^[17]