1.E.19.3.1
The C. difficile holin, TcdE.  TcdE acts as a holin-like protein to facilitate the release of C. difficile toxins A and B to the extracellular environment, but, unlike most phage holins, it does not cause the non-specific release of cytosolic contents. TcdE is thus a bacterial holin that releases toxins into the environment by a phage-like system (Tan et al. 2001; Govind and Dupuy 2012).  Different isoforms have differing activities in toxin release (Govind et al. 2015). An autolysin, Cwp19 (L7PGA3), may also play a role in toxin release (El Meouche and Peltier 2018). Adaptation of this phage-derived holin/endolysin system to toxin transport has been discussed (Mehner-Breitfeld et al. 2018). Thus, TcdE exists as three isoforms, differing with respect to their N-terminal extensions.  The longest TcdE isoform has a moderate effect on cell growth, whereas the shortest isoform strongly induces lysis. The effect of the longest isoform was inhibitory for cell lysis, implying a regulatory function of the N-terminal 24 residues.  Mehner-Breitfeld et al. 2018 analyzed the PaLoc sequence of 44 C. difficile isolates and found that four of these encode only the short TcdE isoform, and the most closely related holins from C. difficile phages only possess one of these initiation codons, indicating that the N-terminal extensions of TcdE evolved in C. difficile.