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1.E.66.  The Phage Mu Holin-like Releasin (Releasin) Family 

Bacteriophage Mu has been shown to have only one lysis gene, the endolysin gp22. This is surprising because lysis by Caudovirales phages usually requires proteins which disrupt all three layers of the cell envelope, a holin, an endolysin, and a spanin targeting the cytoplasmic membrane, peptidoglycan (PG), and outer membrane (OM), respectively, with the holin determining the timing of lysis initiation. Chamblee et al. 2022 found that gp22 is a signal-anchor-release (SAR) endolysin and identified gp23 and gp23.1 as two-component spanin subunits (see TC family 1.M.7). However, Mu lacks a typical holin and instead encodes a membrane-tethered cytoplasmic protein, gp25 (DUF2730), which is required for the release of the SAR endolysin. Mutational analysis showed that this dependence on gp25 is conferred by lysine residues at positions 6 and 7 of the short cytoplasmic domain of gp22. gp25, (a releasin), also facilitates the release of SAR endolysins from other phages. Moreover, the entire length of gp25, including its N-terminal transmembrane domain, belongs to a protein family, DUF2730, found in many Mu-like phages, including those with cytoplasmic endolysins. Mechanism of releasin function as a rationale for Mu lysis without holin control was discussed (Chamblee et al. 2022 ). 

Host cell lysis is the terminal event of the bacteriophage infection cycle. In Gram-negative hosts, lysis requires proteins that disrupt each of the three cell envelope components, only one of which has been identified in Mu: the endolysin gp22. gp22 is a SAR endolysin, a muralytic enzyme that activates upon release from the membrane to degrade the cell wall. Genes 23 and 23.1 are spanin subunits used for outer membrane disruption. But Mu is the first characterized Caudovirales phage to lack a holin, a protein that disrupts the inner membrane and is traditionally known to release endolysins. Instead, a lysis protein, termed the 'releasin', is used by Mu for SAR endolysin release. This is an example of a system where the dynamic membrane localization of one protein is controlled by a secondary protein (Chamblee et al. 2022).

References associated with 1.E.66 family:

Chamblee, J.S., J. Ramsey, Y. Chen, L.T. Maddox, C. Ross, K.H. To, J.L. Cahill, and R. Young. (2022). Endolysin Regulation in Phage Mu Lysis. mBio 13: e0081322. 35471081