title: Proteomic and genomic characterization of highly infectious Clostridium difficile 630 spores.
abstract: Clostridium difficile, a major cause of antibiotic-associated diarrhea, produces highly resistant spores that contaminate hospital environments and facilitate efficient disease transmission. We purified C. difficile spores using a novel method and show that they exhibit significant resistance to harsh physical or chemical treatments and are also highly infectious, with <7 environmental spores per cm(2) reproducibly establishing a persistent infection in exposed mice. Mass spectrometric analysis identified approximately 336 spore-associated polypeptides, with a significant proportion linked to translation, sporulation/germination, and protein stabilization/degradation. In addition, proteins from several distinct metabolic pathways associated with energy production were identified. Comparison of the C. difficile spore proteome to those of other clostridial species defined 88 proteins as the clostridial spore "core" and 29 proteins as C. difficile spore specific, including proteins that could contribute to spore-host interactions. Thus, our results provide the first molecular definition of C. difficile spores, opening up new opportunities for the development of diagnostic and therapeutic approaches.
authors: Microbial Pathogenesis Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom. tl2@sanger.ac.uk
authors: Trevor D
authors: TD
authors: Lawley
authors: Nicholas J
authors: NJ
authors: Croucher
authors: Lu
authors: L
authors: Yu
authors: Simon
authors: S
authors: Clare
authors: Mohammed
authors: M
authors: Sebaihia
authors: David
authors: D
authors: Goulding
authors: Derek J
authors: DJ
authors: Pickard
authors: Julian
authors: J
authors: Parkhill
authors: Jyoti
authors: J
authors: Choudhary
authors: Gordon
authors: G
authors: Dougan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000032:analysis* / Q000235:genetics*; D016360:Clostridioides difficile / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D005798:Genes, Bacterial; D023281:Genomics; D006358:Hot Temperature; D013058:Mass Spectrometry; D051379:Mice; D020543:Proteome / Q000032:analysis*; D013171:Spores, Bacterial / Q000737:chemistry* / Q000235:genetics*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020543:Proteome