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 Ϸ1 ng͞kg. 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 virulencerelated factors could be identified, such as an array of surfacelayer 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.

The genome ofClostridium kluyveri, a strict anaerobe with unique metabolic features

“…The mass fingerprint patterns of the subunits were found to match those predicted from the rnf CDS (data not shown). The function of RnfA-G as NADH:ferredoxin oxidoreductase was first included in a model of the energy metabolism of C. tetani (40). Purification of this membrane enzyme verified this hypothesis (E. Jayamani, C. D. Boiangiu, and W.B., unpublished observations).…”

The genome sequence ofClostridium botulinumtype C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny

“…The genome of c-st is a linear 185,682-bp dsDNA with terminal direct repeats (TDRs) of 404 bp. The average G ϩ C content is 26.2%, slightly lower than those of sequenced Clostridium species (25)(26)(27), Clostridium acetobutylicum (30.9%), Clostridium perfringens (28.6%), and Clostridium tetani (28.6%). We identified 198 ORFs on the phage genome (CST001-198) but no tRNA gene.…”

“…Lysogenization of BoNTX phages as circular plasmids may imply that they have some genetic relationship to the plasmids encoding other types of toxins. Although no recognizable sequence homology was observed between c-st and the tetanus-toxin-encoding plasmid (27), it would be worthwhile to analyze the genome sequences of BoNTX-encoding plasmids.…”

An oligarchic microbial assemblage in the anoxic bottom waters of a volcanic subglacial lake

“…Rather, their over-representation in our libraries may be a consequence of extraction/PCR bias or a high number of rRNA operons per cell. Some members of the Clostridium (in the order Clostridiales along with Acetobacterium) have X10 rRNA operons (Rainey et al, 1996;Brü ggemann et al, 2003;Acinas et al, 2004;Sadeghifard et al, 2006).…”