Phylogenetic and structural overview of the TcdA and TcdB protein family.

(A) The TcdA family forms a monophyletic clade with TcsH from Paeniclostridium sordellii as a sister phylogenetic lineage. Similarly, the TcdB family forms a monophyletic clade with TcsL from Paeniclostridium sordellii as a sister phylogenetic lineage. This implies a scenario whereby TcdA and TcdB evolved by an ancestral gene duplication that predates the speciation event leading to divergence of C. difficile and P. sordellii. (B) Representative crystal structures and domain architectures are shown for TcdA (above) and TcdB (below). The structure of TcdA lacks the CROPS domain and is derived from PDB ID 4F04. The full-length structure of TcdB is based on PDB ID (6OQ5), and was modified to remove bound antibodies. Domain definitions were derived from Aktories et al. [24].

(TIF)