2008 2008 Elsevier Ltd. All rights reserved. Except for filamentous phages, all phages liberate the progeny virions by lysis of the host, and almost all double-stranded DNA viruses use the holin-endolysin mode of lysis. Holins are small phage-encoded membrane proteins that permeabilize the host membrane at a programmed time. Endolysins are muralytic enzymes necessary for degrading the host peptidoglycan. The muralytic action of each phage endolysin is controlled by the holin. In some cases, the endolysin accumulates in the host cytoplasm during the infection cycle, and at a programmed time, the holin molecules trigger to form a 'hole' that allows the endolysin to escape across the membrane and attack the cell wall. In other cases, the endolysin is exported by the host sec system in an inactive form, and holin triggering causes activation of the enzymes as a result of the collapse of the proton-motive force. Endolysins have been found with four different enzyme activities, each of which is directed at one of the three different chemical linkages in the murein. Holins are extremely diverse and fall into at least three different topological classes, with one to three transmembrane domains. In contrast, small single-stranded nucleic acid phages have single gene responsible for lysis and no muralytic activity is elaborated. In two of these cases, the single lysis gene encodes a specific inhibitor of a host enzyme required for murein precursor biosynthesis.
