Double-strand DNA bacteriophages employ the holin-endolysin dyad as core components of different strategies to lyse bacterial hosts. In the so-called canonical model the holin holes play an essential role in lysis as they provide a conduit for passage of the cytoplasm-accumulated endolysin to the cell wall (CW), where it degrades the peptidoglycan. It is considered that once synthesized canonical endolysins immediately acquire their fully active conformation, having thus the capacity to efficiently cleave the peptidoglycan if contact to the CW is allowed. We show here however that holin-mediated cell death may be required to fully sensitize cells to the lytic action of canonical endolysins, a role that is obviously masked by the key function of the holin in endolysin release. We demonstrate that in certain conditions Bacillus subtilis cells are capable of counteracting the activity of the phage SPP1 endolysin attacking the CW either from within or from without. This capacity is lost after holin action or in presence of agents that mimic its membrane-depolarizing role. We have observed a similar relationship between lytic activity and membrane proton motive force for a staphylococcal endolysin. The possible implications of these findings in the exploitation of endolysins as enzybiotics are discussed.
© 2016 John Wiley & Sons Ltd.