Holin-Dependent Secretion of the Large Clostridial Toxin TpeL by <i>Clostridium perfringens</i>

ABSTRACT Large clostridial toxins (LCTs) are secreted virulence factors found in several species, including Clostridioides difficile , Clostridium perfringens Paeniclostridium sordellii and novyi . LCTs large that lack a secretion signal sequence, studies by others have shown the of C. TcdA TcdB, require holin-like protein, TcdE, for secretion. The TcdE gene is located on pathogenicity locus (PaLoc) holin-encoding genes also present LCT-encoded PaLocs from P. However, holin (TpeE) associated with LCT TpeL has no homology different membrane topology than TcdE. In addition, TpeE identical to TatA which core twin-arginine translocation (Tat) system. To determine if was necessary sufficient secrete TpeL, type C strain were expressed A HN13, measured using Western blot methods. We required not due cell lysis. Mutant forms lacking an amphipathic helix charged C-terminal domain failed mutations deleted conserved domains indicated only full-length protein could be secreted. summary, we identified novel family proteins can function, some cases, as system need fold cytoplasm. IMPORTANCE Little known about mechanism Since major pathogens, wanted define previously described secretion-associated holins. discovered member widely dispersed class proteins, TpeL. bears high degree similarity form pore through Tat substrates pass cytoplasmic membrane. Thus, TpeE-TpeL may model understanding holin-dependent but how function process.