We isolate novel bacteriophages from diverse environmental samples. Our screening protocols can distinguish between temperate and lytic phages, ensuring you obtain the specific type required for your study.
Learn MoreBacteriophages, the most abundant biological entities on Earth, exhibit two primary life cycles: the lytic cycle and the lysogenic cycle. Unlike the aggressive replication and immediate host destruction seen in the Lytic Cycle, temperate phages adopting the lysogenic cycle integrate their genome into the host chromosome, establishing a long-term, stable relationship known as lysogeny. This temperate lifestyle allows the phage to replicate passively along with the bacterial host without killing it, until specific environmental cues trigger a switch to lysis. At Creative Biolabs, our comprehensive Phage Services encompass the isolation, characterization, and engineering of both lytic and temperate phages to support your advanced research needs.
Temperate phages possess a unique genetic switch that allows them to choose between two divergent pathways upon infection: the lytic pathway, which results in the production of new virions and cell death, or the lysogenic pathway, which leads to the integration of the phage genome (prophage) into the bacterial chromosome. This decision is not random but is a sophisticated response to the metabolic state of the host cell and the multiplicity of infection (MOI). When host cells are abundant and growing rapidly, the lytic cycle is often favored to maximize viral propagation. Conversely, under conditions of starvation or high phage density, the lysogenic cycle ensures the survival of the phage genome by embedding it within a surviving host.
The establishment of lysogeny relies on the synthesis of a repressor protein (such as the cI repressor in Phage Lambda) that blocks the expression of lytic genes. This repression grants the host bacterium immunity to superinfection by phages of the same type, a phenomenon that has profound implications for bacterial ecology and evolution.
The lysogenic cycle is a highly regulated process involving several distinct stages, from initial infection to the maintenance of the prophage state and eventual induction.
Fig.1 The bacteriophage lysogenic cycle.1,3
Similar to the lytic cycle, the process begins with the specific binding of the phage tail fibers to receptors on the bacterial surface. The phage DNA is then injected into the host cytoplasm. For temperate phages like Lambda, the linear genome typically circularizes immediately upon entry via cohesive ends (cos sites) to protect it from host exonucleases.
Once circularized, a molecular race begins between the expression of lytic promoters and lysogenic promoters. In Phage Lambda, this is controlled by the accumulation of the cII protein. If cII levels are high (often stabilized by poor host metabolic status), it activates the transcription of the integrase gene and the cI repressor, steering the phage toward lysogeny. If cII is degraded by host proteases (active in healthy, dividing cells), the lytic cycle prevails.
If the lysogenic pathway is selected, the phage produces an enzyme called integrase. This enzyme facilitates site-specific recombination between a specific sequence on the phage genome (attP) and a homologous sequence on the bacterial chromosome (attB). The phage DNA is physically inserted into the host genome, becoming a prophage. At this stage, the viral genome is largely silent, expressing only the repressor protein needed to maintain this state.
The prophage is replicated passively along with the bacterial chromosome during cell division. Each daughter cell inherits a copy of the prophage. This vertical transmission allows the phage to persist in the bacterial population without destroying its host. The continuous expression of the repressor protein ensures that the lytic genes remain turned off and prevents infection by other incoming phages of the same immunity group.
The lysogenic state is stable but not permanent. If the host bacterium undergoes DNA damage (e.g., from UV radiation or mitomycin C), the bacterial SOS response is triggered. This activates the host RecA protein, which induces the autocleavage of the phage repressor. With the repressor destroyed, the lytic genes are derepressed. The excisionase enzyme is produced to reverse the integration process, excising the phage DNA from the chromosome. The phage then enters the lytic cycle, producing new virions and lysing the cell to escape the dying host.
While the prophage is dormant regarding viral replication, it is often biologically active in other ways. Many prophages carry "morons"—extra genes that are not essential for the phage life cycle but provide a fitness advantage to the bacterial host. This phenomenon, known as lysogenic conversion, significantly impacts bacterial virulence and evolution.
Whether you are investigating the basic biology of lysogeny or screening for strictly lytic phages for therapeutic applications, Creative Biolabs offers a suite of specialized services tailored to your research.
We isolate novel bacteriophages from diverse environmental samples. Our screening protocols can distinguish between temperate and lytic phages, ensuring you obtain the specific type required for your study.
Learn MoreFor phage therapy candidates, ensuring the absence of lysogeny is critical. We perform rigorous prophage induction tests (mitomycin C, UV) and genomic analysis to confirm the lytic nature of your phages.
Learn MoreWe provide complete genome sequencing and annotation services to identify integrase genes, repressor binding sites, and potential virulence factors encoded within prophage regions.
Learn MoreTemperate phages are excellent vehicles for gene delivery. We offer engineering services to modify lysogenic phages for applications in synthetic biology, including gene circuit delivery and bacterial strain engineering.
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Recent research continues to uncover the complex interplay between host metabolism and phage induction. In a notable study, researchers investigated the mechanism of prophage induction in Staphylococcus aureus triggered by metabolites from coinfecting Pseudomonas aeruginosa. The study demonstrated that pyocyanin, a secondary metabolite produced by P. aeruginosa, acts as a specific inducer of the SOS response in S. aureus, leading to the selective induction of resident prophages. This cross-species interaction highlights the ecological significance of the lysogenic cycle in polymicrobial communities, where chemical warfare between bacteria can inadvertently trigger viral replication bombs. The findings suggest that the stability of the lysogenic state is heavily influenced by the chemical microenvironment, a factor that must be considered in both ecological modeling and therapeutic applications.
Fig.2 Pyocyanin selectively induces phiMBL3 prophage in Staphylococcus aureus (vs Mitomycin C).2,3
Q: Can a lysogenic phage become lytic?
Q: Why are temperate phages generally avoided in phage therapy?
A: Temperate phages are usually avoided because they do not immediately kill the host and can integrate into the bacterial genome. This integration poses risks of horizontal gene transfer, potentially spreading antibiotic resistance or virulence genes (lysogenic conversion) rather than eliminating the pathogen.
Q: How do you detect if a bacterium contains a prophage?
A: Prophages can be detected through whole-genome sequencing (identifying phage-related genes like integrase) or by inducing the culture with agents like mitomycin C and observing plaque formation on a sensitive indicator strain.
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