LAMBDA BACTERIOPHAGE LYSIS-LYSOGENY DECISION

Lambda Bacteriophage Lysis-Lysogeny Decision

Lambda Bacteriophage Lysis-Lysogeny Decision

Introduction

The lysis-lysogeny decision of bacteriophage lambda (?) is a paradigm for developmental genetic networks. There are three key features, which characterize the network. First, after infection of the host bacterium, a decision between lytic or lysogenic development is made that is dependent upon environmental signals and the number of infecting phages per cell. Second, the lysogenic prophage state is very stable. Third, the prophage enters lytic development in response to DNA-damaging agents. (Bandyopadhyay, 2010) The CI and Cro regulators define the lysogenic and lytic states, respectively, as a bistable genetic switch. Whereas CI maintains a stable lysogenic state, recent studies indicate that Cro sets the lytic course not by directly blocking CI expression but indirectly by lowering levels of CII which activates cI transcription.

Discussion

A central challenge in the post genomic era is to understand processes governing the dynamics of highly complex genetic regulatory networks. (Kobiler, 2007) Analysis of such complex systems would be greatly facilitated by similar studies using an ideal paradigm in which most if not all of the elements composing the system were known. Phage ?, the most comprehensively studied bacteriophage, is the prototype of a class of lambdoid phages with whom it shares similar genome organization and functions. Studies of ? that began in the 1950s continue to reveal key molecular processes in gene regulatory mechanisms and development. However, despite years of study, many genetic interactions still remain to be uncovered and those that we already know require reexamination. For an accurate, complete, and quantitative analysis of the genetic network, in particular its temporal progression, these remaining questions need to be addressed. In this review we summarize a systems biology approach to the study of genetic regulatory circuits of phage ?. We define the individual components of the circuits and switches, describe the kinetics of their interactions, and explain how the interactions achieve robustness in the performance of the circuits. We also stress some puzzles that still exist in lambda's regulatory system.

The ? System

Bacteria and their temperate phages, like Escherichia coli and ?, exist in symbiotic relationships. These phages can be present in a dormant, lysogenic (prophage) state replicating passively with the host or they can develop lytically, producing progeny phages and killing their hosts, ? phage infecting an E. coli cell makes a decision to follow either a lytic or a lysogenic pathway (Figure 1). If the lytic pathway is followed, the phage replicates its DNA autonomously, expresses the morphogenetic genes, assembles virions, and lyses the host. If the lysogenic course ensues, a stable lysogen is established in which the prophage is integrated into the host chromosome with lytic gene expression turned off. (Pierre, 2008) The prophage DNA replicates as part of the bacterial genome during subsequent cell divisions, and confers immunity to the cell against infection by another ?. Treatment with DNA-damaging agents, which leads to an SOS response, causes the lysogenic state to irreversibly switch into lytic development, mimicking the lytic ...