Phage lysis: do we have the hole story yet?

•Holins or pinholins form membrane holes upon reaching a critical concentration.•Murein degradation is effected either by cytoplasmic or SAR endolysins.•The outer membrane must be disrupted by two-component or unimolecular spanins.•Lysis proteins are regulated by tertiary, quaternary and topological dynamics.

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.