20971909
not annotated - annotated - LINNAEUS only
Mapping interactions between germinants and Clostridium difficile spores.
Germination of Clostridium difficile spores is the first required step in establishing C. difficile-associated disease (CDAD). Taurocholate (a bile salt) and glycine (an amino acid) have been shown to be important germinants of C. difficile spores. In the present study, we tested a series of glycine and taurocholate analogs for the ability to induce or inhibit C. difficile spore germination. Testing of glycine analogs revealed that both the carboxy and amino groups are important epitopes for recognition and that the glycine binding site can accommodate compounds with more widely separated termini. The C. difficile germination machinery also recognizes other hydrophobic amino acids. In general, linear alkyl side chains are better activators of spore germination than their branched analogs. However, L-phenylalanine and L-arginine are also good germinants and are probably recognized by distinct binding sites. Testing of taurocholate analogs revealed that the 12-hydroxyl group of taurocholate is necessary, but not sufficient, to activate spore germination. In contrast, the 6- and 7-hydroxyl groups are required for inhibition of C. difficile spore germination. Similarly, C. difficile spores are able to detect taurocholate analogs with shorter, but not longer, alkyl amino sulfonic acid side chains. Furthermore, the sulfonic acid group can be partially substituted with other acidic groups. Finally, a taurocholate analog with an m-aminobenzenesulfonic acid side chain is a strong inhibitor of C. difficile spore germination. In conclusion, C. difficile spores recognize both amino acids and taurocholate through multiple interactions that are required to bind the germinants and/or activate the germination machinery.
Ann file
T1 Species 44 65 Clostridium difficile
N1 Reference T1 Taxonomy:1496
T2 Species 90 111 Clostridium difficile
N2 Reference T2 Taxonomy:1496
T3 Species 162 174 C. difficile
N3 Reference T3 Taxonomy:1496
T4 Species 303 315 C. difficile
N4 Reference T4 Taxonomy:1496
T5 Species 438 450 C. difficile
N5 Reference T5 Taxonomy:1496
T6 Species 684 696 C. difficile
N6 Reference T6 Taxonomy:1496
T7 Species 1217 1229 C. difficile
N7 Reference T7 Taxonomy:1496
T8 Species 1260 1272 C. difficile
N8 Reference T8 Taxonomy:1496
T9 Species 1584 1596 C. difficile
N9 Reference T9 Taxonomy:1496
T10 Species 1631 1643 C. difficile
N10 Reference T10 Taxonomy:1496