File:Archetypical Pathogenicity Locus (PaLoc),encoding the large clostridial toxins(LCTs) involved in C. difficile infections CDI.png

English: Figurerepresentsthelocus of 19.8 kb found in C.difficile strain 630, DSM 27543 https://www.dsmz.de/collection/catalogue/details/culture/DSM-27543 , GenBankaccessionnumberAM180355 https://www.ncbi.nlm.nih.gov/nuccore/AM180355 , positions 770.154 to 789.973 bp. Genes depicted (left to right, 5’-3’ downstreamforward) are: 1. tcdD pathogenicity locus conserved protein, coexpressed and found in several operons encoding toxins in other species, with DNA repair and recombination  activityreportedin highlysimilar archaealpeptides and Sigma factor positive regulator.  2. tcdB Clostridium_difficile_toxin_A, a  cytotoxin, a very important protein for virulence. 3. tcdE, an Holin-like protein secretion function. 4. tcdA, Clostridium_difficile_toxin_A , enterotoxin. 5. tcdC, putative peptide (coding reverse) and negative regulator. Toxin B and Toxin A have a similarity at the DNA level. They both a functional toxin protein of 4 domains, encoded in glycosylating enzymatic domain A, autocatalytic processing domain cysteine protease C, translocating domain D and binding C-terminal domain B.  The protein undergoes postransductional modifications and the domains act in synergic effect to achieve pathogenic effects in the cell targeting  Rho family of GTPases https://en.wikipedia.org/wiki/Rho_family_of_GTPases . It must be noted that the loci composition has been found to be variable across different strains. There are clinical isolates not having a functional toxin A (pseudogene), or having a large transposon insertion between toxin A and toxin B, or not having any functional toxin gene. Also there are strains having differences in the 5' regulator, having a pseudogene or small accessory genes.