Protecting The Neighborhood: Extreme Measures

In the unending wars of organism vs. organism, the growth of bacteriophage and the defenses raised by bacteria were among the first recognized and continue to provide new variations and insights on ways to defend oneself. A paper in this issue of the Proceedings demonstrates that prokaryotes, like eukaryotes, have chosen proteolytic self-destruction as a route to protection from attack, albeit a protection for the community rather than for the cell under attack (1). Unleashing a protease that is capable of degrading a vital cell protein is likely to be an irreversible process and thus a somewhat risky proposition, particularly if the vital cell protein is one involved in protein synthesis, therefore blocking new synthesis of the degraded protein. Nonetheless, it is a strategy that is proving to be common. The cascade of caspases, the proteases that lead to programmed cell death both as part of developmental programs and in response to an enormous variety of insults is one increasingly popular example of intracellular proteolysis as endgame (2). Plants resist pathogens in part through a hypersensitive response, a programmed cell death of the infected cell that presumably limits further pathogen growth, although it remains to be seen whether similar proteases participate in this process (3). Georgiou et al. (1) have reconstructed in vitro the protease-based exclusion system that limits growth of the lytic bacteriophage T4 in certain strains of Escherichia coli. Protection is provided by killing the host before T4 has a chance to fully develop a burst of infecting phage. This is accomplished, in part, by cleavage of the translation elongation factor Tu (EF-Tu), essential for protein synthesis. The putative protease, Lit, is encoded by a cryptic prophage-like element called e14 found in some but not all E. coli strains. Obviously, expressing both an active protease …