Bacteriophages (“eaters of bacteria”) are viruses which infect prokaryotes. Although bacteriophages are very diverse and there are lots of ways of dividing them up, one way is to consider their pattern of replication. When a virulent phage infects a host cell, the inevitable result is lysis of the cell and the release of a crop of new phage particles. Temperate phages are more subtle and can replicate in one of two ways, either by lysing the host cell in the same way as a virulent phage, or by entering into a state called lysogeny, where only a few phage genes are expressed and the phage genome is replicated along with that of the host and transmitted to new cells as they divide.
Bacteriophage lambda has been studied for over 50 years and has served as a model for understanding gene expression. Lambda is a temperate phage capable of undergoing two developmental pathways: lysis or lysogeny. Lytic development is lethal to host the Escherichia coli, resulting in amplification and release of progeny phage. In the lysogenic state the phage integrates into the host chromosome, where it can silence its lytic promoters and replicate quiescently as a prophage. Induction of lysis from the lysogenic state can be triggered by agents which damage DNA or interfere with replication, such as mitomycin C or UV light. The gene regulatory network underlying the lambda life cycle has been studied in exhaustive detail, yet the switch continues to reveal new levels of complex regulation (Ptashne M: A Genetic Switch: Phage Lambda Revisited, 3rd Ed: Cold Spring Harbor Laboratory Press; 2004).
In the lysogenic state lambda expresses a small set of proteins that, among other things, repress lysis and confer fitness to the host while altering little else in terms of host functions. This makes sense since advancing host fitness favours survival of the prophage. On the other hand, during lytic growth the phage has no such concern for the host cell, other than a selection pressure to maintain host infrastructure for producing new progeny phage.
A recent paper uses the latest technology to investigate how host cell functions are modulated by the lambda gene expression program (Global analysis of host response to induction of a latent bacteriophage. BMC Microbiology 2007 7: 82). To address this question, the authors examined the effect of prophage induction on host cell physiology. Since much of the lambda regulatory circuitry is controlled at the transcriptional level, they surveyed gene expression profiles of Escherichia coli and lambda phage transcriptomes throughout the time course of prophage induction by UV light. They did this by constructing a whole-genome E. coli/lambda phage DNA microarray, representing 99% of 4,290 E. coli open reading frames and 66 predicted lambda open reading frames. They then characterized the response of lysogenic E. coli carrying lambda prophage and non-lysogenic cells to UV light, and by comparing the differences in gene expression, were able to study the impact of prophage induction on phage and host gene expression.
As expected, they found a temporally-coordinated program of phage gene expression, with distinct early, middle and late transcription classes. The study confirmed known host-phage interactions, including induction of expression of heat shock genes and suppression of genes involved in cell division and initiation of replication. They were able to identify 728 E. coli genes which responded to prophage induction, which included various stress response pathways and global transcription regulators. Several hundred genes involved in central metabolism, energy metabolism, translation and transport were down-regulated during the late stage of phage induction. Although statistically significant, most of the changes in gene expression were mild, with only 140 genes showing greater than two-fold change.
Overall, this study provides the first global dynamic picture of how host processes respond to lambda phage induction. It is surprising how low the impact of prophage induction is on host cell physiology.
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