Lambda phage

Enterobacteria phage λ (lambda phage, coliphage λ, officially Escherichia virus Lambda) is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli (E. coli).

[2] The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring.

Usually, a "lytic cycle" ensues, where the lambda DNA is replicated and new phage particles are produced within the cell.

The tail of lambda phages is made of at least 6 proteins (H, J, U, V, Stf, Tfa) and requires 7 more for assembly (I, K, L, M, Z, G/T).

Low temperature, starvation of the cells and high multiplicity of infection (MOI) are known to favor lysogeny (see later discussion).

This is the lifecycle that the phage follows following most infections, where the cII protein does not reach a high enough concentration due to degradation, so does not activate its promoters.

O and P are responsible for initiating replication, and Q is another antiterminator that allows the expression of head, tail, and lysis genes from PR’.

Gam is also important in that it inhibits the host RecBCD nuclease from degrading the 3’ ends in rolling circle replication.

[18] The lysogenic lifecycle begins once the cI protein reaches a high enough concentration to activate its promoters, after a small number of infections.

In response to stress, the activated prophage is excised from the DNA of the host cell by one of the newly expressed gene products and enters its lytic pathway.

The sequence of the bacterial att site is called attB, between the gal and bio operons, and consists of the parts B-O-B', whereas the complementary sequence in the circular phage genome is called attP and consists of the parts P-O-P'.

Both Int and IHF bind to attP and form an intasome, a DNA-protein-complex designed for site-specific recombination of the phage and host DNA.

Any situation where a lysogen undergoes DNA damage or the SOS response of the host is otherwise stimulated leads to induction.

[22] Prophage reactivation in phage λ appears to occur by a recombinational repair process similar to that of MR.

The repressor found in the phage lambda is a notable example of the level of control possible over gene expression by a very simple system.

This autonegative regulation ensures a stable minimum concentration of the repressor molecule and, should SOS signals arise, allows for more efficient prophage induction.

The latter is determined solely by the activation of RecA in the SOS response of the cell, as detailed in the section on induction.

The former will also be affected by this; a cell undergoing an SOS response will always be lysed, as no cI protein will be allowed to build up.

cIII appears to stabilize cII, both directly and by acting as a competitive inhibitor to the relevant proteases.

Computer modeling and simulation suggest that random processes during infection drive the selection of lysis or lysogeny within individual cells.

[28] Some of its uses include its application as a vector for the cloning of recombinant DNA; the use of its site-specific recombinase (int) for the shuffling of cloned DNAs by the gateway method;[29] and the application of its Red operon, including the proteins Red alpha (also called 'exo'), beta and gamma in the DNA engineering method called recombineering.

Lambda phage will enter bacteria more easily than plasmids, making it a useful vector that can either destroy or become part of the host's DNA.

[31] Lambda phage can also be manipulated and used as an anti-cancer vaccine that targets human aspartyl (asparaginyl) β-hydroxylase (ASPH, HAAH), which has been shown to be beneficial in cases of hepatocellular carcinoma in mice.

Bacteriophage Lambda Structure at Atomic Resolution [ 1 ]
The bacteriophage lambda virion
Bacteriophage lambda virion (schematic). Protein names and their copy numbers in the virion particle are shown. The presence of the L and M proteins in the virion is still unclear. [ 5 ]
Linear layout of lambda phage genome with major operons, promoter regions and capsid coding genes. [ 5 ]
Lambda phage J protein interaction with the LamB porin
Lambda phage DNA injection into the cell membrane using Mannose PTS permease (a sugar transporting system) as a mechanism of entry into the cytoplasm
Early activation events involving N protein
Lysis plaques of lambda phage on E. coli bacteria
Diagram showing the retro-regulation process that yields a higher concentration of xis compared to int. The mRNA transcript is digested by bacterial RNase starting from the cleaved hairpin loop at sib.
A simplified representation of the integration/excision paradigm and the major genes involved.
Lysogen repressors and polymerase bound to OR1 and recruits OR2, which will activate PRM and shutdown PR.
Transcriptional state of the P RM and P R promoter regions during a lysogenic state vs induced, early lytic state.
The function of LexA in the SOS response. LexA expression leads to inhibition of various genes including LexA.
Protein interactions that lead to either Lytic or Lysogenic cycles for Lambda phage
Visual representation of repressor tetramer/octamer binding to phage lambda L and R operator sites (stable lysogenic state)
Diagram of temperate phage life cycle, showing both lytic and lysogenic cycles.