Phage lysis: do we have the hole story yet?

In infections of Gram-negative bacteria, lysis is a three step process, with a choice of two effectors for each step. At a precise, allele-specific time, the inner membrane (IM) is fatally permeabilized by either a holin or a pinholin. This allows a muralytic enzyme, either a canonical endolysin, escaping from the cytoplasm, or a SAR endolysin, activated in the periplasm, to degrade the peptidoglycan. Surprisingly, a third class of lysis protein, the spanin, is required for disruption of the outer membrane (OM). Key steps are regulated by membrane protein dynamics, both in terms of bilayer topology and subcellular distribution, by the energization of the membrane, and by holin-specific inhibitors called antiholins.