Review: Can phages have a third life cycle?

Have you ever heard of bacteriophages (phages)? If yes, then what about Pseudolysogeny?

The two words are in one way or the other interconnected though the latter is experienced through the former. Phages are referred to as viruses that are naturally enemies to bacteria. Phages are abundant in the environment with their number far more than that of all other organisms combined (including bacteria). Phages are tiny in their structure, exhibit single or double-stranded DNA or RNA, and sometimes undergo three categories of their lifecycle. The commonly known two cycles are lytic (involves bacterial lysis) or lysogenic (virions are transmitted to daughter cells). However, the third cycle known as Pseudolysogeny is poorly understood and not commonly studied by scientists.

Pseudolysogeny was first described by Baess (1971) as an unstable interaction that is not productive but eventually resolves into true lysogeny or virulent growth. Later, it was modified by Los & Wegrzyn (2012) as a stage in the phage development, without multiplication of the genome or its replication synchronized with the cell cycle and stable maintenance in the cell line that allows subsequent restart and resumption of the virus cycle. Some scientists define Pseudolysogeny as a form of phage-host cell interaction in which the nucleic acid of the phage resides within its starved host in an unstable and inactive state. Temperate phages show this as an intermediate stage between the lytic and lysogeny cycles which allows bacteria to survive infections.

The phage replication cycles. Schematic of lytic, lysogenic, and pseudolysogenic cycles. a | Lytic phages immediately enter a productive cycle, in which the phage genome is replicated and phage capsid and tail proteins are synthesized using bacterial cell pieces of machinery; the phage genome is then packaged into progeny phage particles, which are liberated via bacterial lysis. b | Temperate phages enter a lysogenic cycle, in which the phage genome is integrated into the bacterial chromosome (becoming a prophage) and persists in what is considered a phage latent or dormant state that does not promote cell death or production of phage particles. Prophages are replicated together with the bacterial host chromosome during host cell replication and switch into lytic production upon exposure to DNA damage (not shown). c | Pseudolysogeny is an unstable situation in which the phage genome fails to replicate (as in lytic production) or become established as a prophage (as in lysogeny). Pseudolysogeny occurs most frequently under nutrient-deprived conditions when bacterial cells cannot support DNA replication or protein synthesis. In this situation, the phage genome remains for an extended period of time as a non-integrated preprophage, which resembles an episome, until the nutritional status is restored, at which point the phage enters either a lysogenic or a lytic life cycle. Importantly, the pseudolysogenic preprophage does not replicate and so is only inherited by one of the daughter cells following cell division (not shown). photo by Feiner Et al (2015)

Pseudolysogeny occurs due to the cell’s highly starved condition in which there is insufficient energy available for the phage to initiate genetic expression leading to either a true temperate response or to the lytic response. In presence of nutrients, the pseudolysogenic state is resolved, resulting in either the establishment of true lysogeny or the initiation of the lytic production of progeny virions. This state explains the long-term survival of viruses in unfavorable environments. Pseudolysogeny is associated with a relatively short half-life of the virions that result.

This cycle has been described by Ackermann and Dubow as a condition involving a constant production of phage in the presence of high host cell abundance. This might be the result of a mixture of sensitive and resistant host cells and/or a mixture of temperate and virulent phages. Pseudolysogeny resembles true lysogeny but the phage genome does not integrate into host cellular replicons as the case with the former.

Pseudolysogeny has been documented in slowly growing cells, for example in P. aeruginosa, two phages are responsible for generalized transduction: F116 (a temperate phage) and UT1 (a virulent phage). Other pseudolysogenic phages include; Escherichia coli phage T4.

The advantages of Pseudolysogenic behavior

Protects the phage nucleic acids against the harsh conditions outside the host.
It is a mechanism to overcome a starved host by preventing an abortive replication or integration event due to a lack of resources.
There is the ability of the temperate phage to prevent being entirely dependent on the host’s DNA damage response to escape from hibernation,

It enables high phage titers to be found in environments where bacterial growth is low and unsupportive for massive phage production due to a lack of nutrients.