title: Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism.
abstract: BACKGROUND
  Clostridium difficile is an anaerobic, Gram-positive bacterium that can reside as a commensal within the intestinal microbiota of healthy individuals or cause life-threatening antibiotic-associated diarrhea in immunocompromised hosts. C. difficile can also form highly resistant spores that are excreted facilitating host-to-host transmission. The C. difficile spo0A gene encodes a highly conserved transcriptional regulator of sporulation that is required for relapsing disease and transmission in mice.
  
  
  RESULTS
  Here we describe a genome-wide approach using a combined transcriptomic and proteomic analysis to identify Spo0A regulated genes. Our results validate Spo0A as a positive regulator of putative and novel sporulation genes as well as components of the mature spore proteome. We also show that Spo0A regulates a number of virulence-associated factors such as flagella and metabolic pathways including glucose fermentation leading to butyrate production.
  
  
  CONCLUSIONS
  The C. difficile spo0A gene is a global transcriptional regulator that controls diverse sporulation, virulence and metabolic phenotypes coordinating pathogen adaptation to a wide range of host interactions. Additionally, the rich breadth of functional data allowed us to significantly update the annotation of the C. difficile 630 reference genome which will facilitate basic and applied research on this emerging pathogen.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Pettit
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Browne
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.forename: Wiep Klaas
authors.initials: WK
authors.lastname: Smits
authors.forename: Robert P
authors.initials: RP
authors.lastname: Fagan
authors.forename: Lars
authors.initials: L
authors.lastname: Barquist
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Martin
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.forename: Sylvia H
authors.initials: SH
authors.lastname: Duncan
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Flint
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Jyoti S
authors.initials: JS
authors.lastname: Choudhary
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK. tl2@sanger.ac.uk.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lawley
mesh_terms: D002087:Butyrates / Q000378:metabolism; D016360:Clostridioides difficile / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D005947:Glucose / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D009154:Mutation; D020543:Proteome; D040901:Proteomics; D013171:Spores, Bacterial; D059467:Transcriptome; D014774:Virulence / Q000235:genetics
chemical_list: D002087:Butyrates; D020543:Proteome; D005947:Glucose