Lytic vs Lysogenic – Understanding Bacteriophage Life Cycles

Figure 2: Depiction of the stages of the bacteriophage lytic cycle. Credit: Technology Networks

Watch the lytic cycle in action here.

Lysogenic cycle

The lysogenic cycle (Figure 3), sometimes referred to as temperate or non-virulent infection, does not kill the host cell, instead using it as a refuge where it exists in a dormant state. Following the injection of the phage DNA into the host cell, it integrates itself into the host genome, with the help of phage-encoded integrases, where it is then termed a prophage. The prophage genome is then replicated passively along with the host genome as the host cell divides for as long as it remains there and does not form the proteins required to produce progeny. As the phage genome is generally comparatively small, the bacterial hosts are normally relatively unharmed by this process.

Figure 3: Depiction of the stages of the bacteriophage lysogenic cycle. Credit: Technology Networks

Transition from lysogenic to lytic

If a bacterium containing prophage is exposed to stressors, such as UV light, low nutrient conditions, or chemicals like mitomycin C, prophage may spontaneously extract themselves from the host genome and enter the lytic cycle in a process called induction.

This process, however, is not perfect and prophage may sometimes leave portions of their DNA behind or take portions of host DNA with them when they re-circularize. If they then infect a new host cell, they may transport bacterial genes from one strain to another in a process called transduction. This is one method by which antibiotic resistance genes, toxin and superantigen-encoding genes and other virulence traits may spread through a bacterial population.

Recent work has shown that transition between lytic and lysogenic infection is also dependent on the abundance of phage in an area as they are able to produce and sense small peptides in a process akin to quorum sensing.⁴

Bacterial immunity to phage infection

Not all bacteria are helpless against phage attack, possessing an “immune system” that allows them to fight back. CRISPR-Cas, which is now synonymous with genetic modification, was first proposed as a bacterial “adaptive immune system” by Francisco Mojica and independently by a group from Université Paris-Sud in 2005.^5,6 The CRISPR locus is an array of short repeated sequences separated by spacers with unique sequences. These spacer sequences were found to have homology to viral and plasmid DNA, including phage. When attacked by a previously unencountered phage, new spacers are added at one side of the CRISPR, making the CRISPR a chronological record of the phage the cell and its ancestors have encountered. In response to phage invasion, the CRISPR sequences are transcribed and, in partnership with Cas proteins, target and destroy the phage sequences that are homologous to the spacers sequences.

Phage as genetic and molecular biology tools

The Lambda phage, originally isolated from Escherichia coli, is one of the best studied phage and formed the basis of many genetic tools. It has even been said that the use of phage as tools ultimately led to the development of molecular biology as a discipline.⁷ In the 1950s, the phage’s ability to recombine with host DNA was first exploited to manipulate the genomes of Salmonella species and so the process of transduction was born.⁸ Since then, it has been used as a vehicle to move genetic material between many organisms, including fungal gene manipulations and even human genes.⁹ It was thanks to the humble phage that human insulin was first safely and cheaply produced. It has also opened up applications in high throughput screening of clones, nanomaterial development, antibacterial treatment for food items, as a diagnostic tool and drug discovery and delivery systems.^10,11

The phage ϕX174 became an unwitting pioneer in 1977 when it was the first organism to have its entire nucleotide sequence determined thanks to Fred Sanger and colleagues.¹²

Phage therapy

Prior to the discovery of antibiotics by Alexander Fleming in 1928, phage were being explored as a method for treating bacterial infections. In the post-antibiotic era, the convenient broad-spectrum activity of antibiotic treatment meant that in most organization’s research into phage therapy was abandoned. However, in many of the former Soviet nations where there was a lack of western antibiotics, research into phage therapies continued through necessity. With the increasing global problems of antibiotic resistance, there has been a resurgence in the phage therapy field in recent years. Whilst phage are able to infect and destroy bacteria and have been successfully used to treat life-threatening infection, their species and even strain specificity and potential for pre-existing immunity of some bacteria mean targeting a phage treatment is currently not a trivial process and must be tailored to the individual infection.¹³ This makes it costly and lengthy. Consequently, it is currently a last resort and there is still much work required in this field.

The phage family tree

With the increasing availability and affordability of nucleotide sequencing, there has been an explosion in the numbers of phage genomes submitted to databases over the past two decades.¹⁴ 

Phage are classified by the International Committee on Taxonomy of Viruses (ICTV), as of their 2017 update, there are 19 families of phage that infect bacteria and archaea (Table 1) but as more samples from more remote areas are sequenced this is only likely to grow in the future.

Table 1: ICTV taxonomic classification of bacteriophage infecting bacteria and archaea.

For mobile users, scroll left and right to view the table data below.