title: The genome sequence of Clostridium tetani, the causative agent of tetanus disease.
abstract: Tetanus disease is one of the most dramatic and globally prevalent diseases of humans and vertebrate animals, and has been reported for over 24 centuries. The manifestation of the disease, spastic paralysis, is caused by the second most poisonous substance known, the tetanus toxin, with a human lethal dose of approximately 1 ng/kg. Fortunately, this disease is successfully controlled through immunization with tetanus toxoid; nevertheless, according to the World Health Organization, an estimated 400,000 cases still occur each year, mainly of neonatal tetanus. The causative agent of tetanus disease is Clostridium tetani, an anaerobic spore-forming bacterium, whose natural habitat is soil, dust, and intestinal tracts of various animals. Here we report the complete genome sequence of toxigenic C. tetani E88, a variant of strain Massachusetts. The genome consists of a 2,799,250-bp chromosome encoding 2,372 ORFs. The tetanus toxin and a collagenase are encoded on a 74,082-bp plasmid, containing 61 ORFs. Additional virulence-related factors could be identified, such as an array of surface-layer and adhesion proteins (35 ORFs), some of them unique to C. tetani. Comparative genomics with the genomes of Clostridium perfringens, the causative agent of gas gangrene, and Clostridium acetobutylicum, a nonpathogenic solvent producer, revealed a remarkable capacity of C. tetani: The organism can rely on an extensive sodium ion bioenergetics. Additional candidate genes involved in the establishment and maintenance of a pathogenic lifestyle of C. tetani are presented.
authors.affiliation: Göttingen Genomics Laboratory and Department of General Microbiology, Institute of Microbiology and Genetics, Georg-August-University, Grisebachstrasse 8, D-37077 Göttingen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Bruggemann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Baumer
authors.forename: Wolfgang Florian
authors.initials: WF
authors.lastname: Fricke
authors.forename: Arnim
authors.initials: A
authors.lastname: Wiezer
authors.forename: Heiko
authors.initials: H
authors.lastname: Liesegang
authors.forename: Iwona
authors.initials: I
authors.lastname: Decker
authors.forename: Christina
authors.initials: C
authors.lastname: Herzberg
authors.forename: Rosa
authors.initials: R
authors.lastname: Martinez-Arias
authors.forename: Rainer
authors.initials: R
authors.lastname: Merkl
authors.forename: Anke
authors.initials: A
authors.lastname: Henne
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gottschalk
mesh_terms: D003017:Clostridium tetani / Q000235:genetics* / Q000472:pathogenicity*; D016680:Genome, Bacterial; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D015398:Signal Transduction; D013742:Tetanus / Q000235:genetics; D037521:Virulence Factors
chemical_list: D037521:Virulence Factors