Brüggemann Holger, Gottschalk Gerhard
Göttingen Genomics Laboratory, Institute of Microbiology and Genetics, Georg-August-University, Grisebachstr. 8, D-37077 Göttingen, Germany.
Anaerobe. 2004 Apr;10(2):53-68. doi: 10.1016/j.anaerobe.2003.08.001.
The decryption of prokaryotic genome sequences progresses rapidly and provides the scientific community with an enormous amount of information. Clostridial genome sequencing projects have been finished only recently, starting with the genome of the solvent-producing Clostridium acetobutylicum in 2001. A lot of attention has been devoted to the genomes of pathogenic clostridia. In 2002, the genome sequence of C. perfringens, the causative agent of gas gangrene, has been released. Currently in the finishing stage and prior to publication are the genomes of the foodborne botulism-causing C. botulinum and of C. difficile, the causative agent of a wide spectrum of clinical manifestations such as antibiotic-associated diarrhea. Our team sequenced the genome of neuropathogenic C. tetani, a Gram-positive spore-forming bacterium predominantly found in the soil. In deep wound infections it occasionally causes spastic paralysis in humans and vertebrate animals, known as tetanus disease, by the secretion of potent neurotoxin, designated tetanus toxin. The toxin blocks the release of neurotransmitters from presynaptic membranes of interneurons of the spinal cord and the brainstem, thus preventing muscle relaxation. Fortunately, this disease is successfully controlled through immunization with tetanus toxoid, a formaldehyde-treated tetanus toxin, but nevertheless, an estimated 400,000 cases still occur each year, mainly of neonatal tetanus. The World Health Organization has stated that neonatal tetanus is the second leading cause of death from vaccine preventable diseases among children worldwide. This minireview focuses on an analysis of the genome sequence of C. tetani E88, a vaccine production strain, which is a toxigenic non-sporulating variant of strain Massachusetts. The genome consists of a 2,799,250 bp chromosome encoding 2618 open reading frames. The tetanus toxin is encoded on a 74,082 kb plasmid, containing 61 genes. Additional virulence-related factors as well as an insight into the metabolic strategy of C. tetani with regard to its pathogenic phenotype will be presented. The information from other clostridial genomes by means of comparative analysis will also be explored.
原核生物基因组序列的解密进展迅速，为科学界提供了大量信息。梭菌基因组测序项目直到最近才完成，始于2001年产溶剂丙酮丁醇梭菌的基因组测序。致病性梭菌的基因组受到了很多关注。2002年，气性坏疽病原体产气荚膜梭菌的基因组序列被公布。目前处于完成阶段且即将发表的是引起食源性肉毒中毒的肉毒梭菌以及艰难梭菌的基因组，艰难梭菌是多种临床表现（如抗生素相关性腹泻）的病原体。我们的团队对神经致病性破伤风梭菌的基因组进行了测序，破伤风梭菌是一种革兰氏阳性产芽孢细菌，主要存在于土壤中。在深部伤口感染中，它偶尔会通过分泌强效神经毒素（即破伤风毒素），在人类和脊椎动物中引起痉挛性麻痹，即破伤风病。该毒素会阻止脊髓和脑干中间神经元突触前膜释放神经递质，从而阻止肌肉松弛。幸运的是，通过用破伤风类毒素（一种经甲醛处理的破伤风毒素）进行免疫接种，这种疾病得到了成功控制，但尽管如此，每年估计仍有40万例病例发生，主要是新生儿破伤风。世界卫生组织指出，新生儿破伤风是全球儿童中可通过疫苗预防疾病导致死亡的第二大主要原因。本综述重点分析了破伤风梭菌E88（一种疫苗生产菌株）的基因组序列，它是马萨诸塞菌株的产毒非芽孢形成变体。该基因组由一条2,799,250 bp的染色体组成，编码2618个开放阅读框。破伤风毒素由一个74,082 kb的质粒编码，该质粒包含61个基因。还将介绍其他与毒力相关的因素以及对破伤风梭菌致病表型代谢策略的深入了解。还将通过比较分析探索来自其他梭菌基因组的信息。
