title: Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci.
abstract: BACKGROUND
  Clostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised.
  
  
  RESULTS
  Phylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied.
  
  
  CONCLUSIONS
  Genome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.
authors.affiliation: Department of Life Sciences, Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK. e.couchman11@imperial.ac.uk.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Couchman
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK. hb4@sanger.ac.uk.
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Browne
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK. md3@sanger.ac.uk.
authors.forename: Matt
authors.initials: M
authors.lastname: Dunn
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK. tl2@sanger.ac.uk.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lawley
authors.affiliation: Department of Veterinary Science and Microbiology, University of Arizona, Tucson, USA. gsonger@gmail.com.
authors.forename: J Glenn
authors.initials: JG
authors.lastname: Songer
authors.affiliation: Anaerobe Reference Laboratory, University Hospital of Wales, Cardiff, UK. val.hall@wales.nhs.uk.
authors.forename: Val
authors.initials: V
authors.lastname: Hall
authors.affiliation: Veterinary Laboratories Agency, Addlestone, Surrey, UK. liljana.petrovska@ahvla.gsi.gov.uk.
authors.forename: Liljana
authors.initials: L
authors.lastname: Petrovska
authors.affiliation: Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia. callum.vidor@monash.edu.
authors.forename: Callum
authors.initials: C
authors.lastname: Vidor
authors.affiliation: Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia. milena.awad@monash.edu.
authors.forename: Milena
authors.initials: M
authors.lastname: Awad
authors.affiliation: Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia. dena.lyras@monash.edu.
authors.forename: Dena
authors.initials: D
authors.lastname: Lyras
authors.affiliation: Department of Life Sciences, Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK. n.fairweather@imperial.ac.uk.
authors.forename: Neil F
authors.initials: NF
authors.lastname: Fairweather
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics*; D002874:Chromosome Mapping; D047989:Paraclostridium sordellii / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D022761:Gene Transfer, Horizontal; D056426:Genetic Loci / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D009439:Neuraminidase / Q000235:genetics; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D010738:Type C Phospholipases / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001427:Bacterial Toxins; D037521:Virulence Factors; D010738:Type C Phospholipases; D009439:Neuraminidase