Bacteriophage lambda (lambda phage) is a temperate bacteriophage that infects Escherichia coli (E. coli). It is one of the most extensively studied organisms in molecular biology and has served as a foundational model for understanding gene regulation, recombination, and transcription. Discovered by Esther Lederberg in 1951, phage lambda has since become an indispensable tool in genetic engineering, cloning, and library construction. At Creative Biolabs, we leverage the unique properties of lambda phage to offer comprehensive Phage Services, ranging from display technology to genomic modification, supporting researchers worldwide in their quest for novel therapeutics and biological insights.
Unlike obligate lytic phages like T4 Phage or T7 Phage, lambda phage possesses the ability to choose between two distinct life cycles: the lytic pathway and the lysogenic pathway. This duality is governed by a complex genetic switch that remains a paradigmatic example of gene regulation. Furthermore, its capacity to package large DNA inserts makes it superior to M13 Phage or MS2/RNA Phage for specific genomic library applications.
The morphology of phage lambda is characteristic of the Siphoviridae family. It features an isometric icosahedral head (capsid) approximately 60 nm in diameter, which encapsulates the viral genome. Attached to the head is a long, flexible, non-contractile tail measuring about 150 nm in length. The tail terminates in a single tail fiber, which is responsible for recognizing and binding to the specific receptor on the surface of the E. coli host cell, known as the lamB porin (maltose receptor).
Fig.1 Lambda bacteriophage structure.1
The lambda genome consists of a double-stranded DNA (dsDNA) molecule approximately 48,502 base pairs in length. A unique feature of the lambda genome is the presence of 12-base single-stranded overhangs at the 5' ends of the linear DNA molecule. These cohesive ends, known as cos sites, are complementary to each other. Upon entering the host cell, the linear DNA circularizes via the annealing of these cos sites, forming a circular episome that serves as the template for transcription and replication.
The defining characteristic of lambda bacteriophage is its ability to follow one of two developmental pathways upon infection. This decision is controlled by a genetic switch involving the competition between two repressor proteins: the lambda repressor (cI) and the Cro protein.
Fig.2 The life cycle of lambda bacteriophage.2
In the lytic cycle, the phage hijacks the host's cellular machinery to replicate its DNA and synthesize viral proteins. The genome is replicated via rolling-circle replication, producing long concatemers of DNA. Structural proteins are synthesized, and the DNA is packaged into new phage heads. Finally, the host cell is lysed by phage-encoded enzymes (holin and endolysin), releasing approximately 100 new virions to infect adjacent cells. This pathway is favored when the host cell is growing rapidly and resources are abundant.
The lambda phage lysogenic cycle represents a state of dormancy and integration. Instead of killing the host, the phage DNA integrates into the bacterial chromosome at a specific attachment site (attB) using the phage-encoded integrase enzyme. Once integrated, the viral genome is termed a "prophage." In this state, the expression of most phage genes is silenced by the cI repressor, which binds to the operator regions and blocks transcription of lytic genes.
The prophage is replicated passively along with the bacterial chromosome during cell division, ensuring that all daughter cells carry the viral genome. This state is extremely stable but can be reversed. If the host cell undergoes stress (e.g., UV radiation or DNA damage), the RecA protein is activated, leading to the cleavage of the cI repressor. This "SOS response" flips the genetic switch, excising the prophage from the genome and initiating the lytic cycle.
The versatile biology of lambda phage has been harnessed for numerous biotechnological applications.
Lambda vectors are widely used for cloning large DNA fragments (up to 25 kb) that are too large for plasmid vectors. Replacement vectors allow the substitution of non-essential phage genes ("stuffer" fragments) with foreign DNA, making them ideal for constructing genomic libraries.
While M13 is common for peptides, lambda display is superior for displaying high-density or multivalent proteins. The lambda capsid allows for the display of multiple copies of larger proteins without disrupting virion assembly, facilitating the selection of high-avidity binders.
The Lambda Red system (involving Exo, Beta, and Gam proteins) facilitates efficient homologous recombination in E. coli. This technology enables precise gene knockouts, insertions, and modifications directly on the bacterial chromosome or on BACs.
Extracts containing lambda packaging proteins are used to package recombinant DNA into viral particles in vitro. This high-efficiency transduction method is a standard step in the construction of cDNA and genomic libraries.
Explore our specialized services tailored for lambda phage research and application:
We provide expert services in constructing robust lambda phage display systems for the screening of peptides, antibodies, and protein domains. Our platform ensures high-efficiency display and reliable library performance.
Learn More →Leveraging lambda vectors, we construct high-quality genomic and cDNA libraries. Our proprietary packaging extracts guarantee high titers and diverse representation of the source material.
Learn More →Utilizing Next-Generation Sequencing (NGS), we offer complete genome sequencing and annotation for novel bacteriophages, including lambda-like variants, to identify essential genes and regulatory elements.
Learn More →We produce high-purity lambda-derived enzymes, including endolysins and holins, which have significant potential as antimicrobial agents against Gram-negative bacteria.
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In a pivotal 2024 study published in Nature Communications, researchers revealed the high-resolution cryo-electron microscopy (cryo-EM) structures of the bacteriophage lambda tail in complex with its host receptor, LamB. This work elucidates the precise molecular mechanism of infection initiation, demonstrating significant conformational changes in the phage tail tip upon binding to the Shigella sonnei 3070 LamB receptor. The study captures the bacteriophage lambda tail in both its closed central tail fiber state and the open state induced by receptor interaction, providing a detailed structural basis for the irreversible adsorption and subsequent DNA ejection process.
Fig.3
Structure of bacteriophage lambda tail interacting with LamB.3
Q: What is the main difference between the lytic and lysogenic cycles?
Q: Why is lambda phage preferred for genomic library construction?
A: Lambda vectors can accommodate larger DNA inserts (up to 25 kb) compared to standard plasmids. Additionally, the in vitro packaging efficiency of lambda phage is very high, allowing for the generation of libraries with high coverage and diversity.
Q: How does the lambda repressor (cI) work?
A: The cI repressor binds to specific operator sequences in the phage genome, preventing the transcription of genes required for the lytic cycle. This maintains the phage in the lysogenic state. Cleavage of cI during the SOS response allows lytic gene expression to resume.
Q: Can lambda phage infect humans?
A: No, bacteriophage lambda is specific to E. coli bacteria and cannot infect human cells. It is considered safe for use in laboratory environments (Biosafety Level 1).
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